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News Article | December 14, 2016
Site: www.nature.com

To obtain a crystal structure of human CCR9, a thermostabilized receptor (StaR) was generated8, 9 containing eight amino-acid substitutions (Extended Data Figs 1 and 2). These modifications did not alter vercirnon binding properties of the receptor compared with wild-type (Extended Data Fig. 3); however, stabilization with the [3H]vercirnon antagonist precludes G-protein coupling of the final StaR (Data not shown). To further facilitate crystallization, amino (N) and carboxy (C) termini were truncated resulting in the construct designated CCR9-StaR(25-340). No fusion partner(s) were used to aid crystallization, and the receptor was crystallized in lipidic cubic phase (LCP) in the presence of the antagonist vercirnon10 (4-tert-butyl-N-{4-chloro-2-[(1-oxidopyridin-4-yl)carbonyl]phenyl}benzenesulfonamide, GSK1605786, CCX282-B). The structure was determined to 2.8 Å resolution with two copies in the asymmetric unit arranged in a parallel fashion with TM4–TM4-mediated interactions (Extended Data Fig. 4). Details of data collection and refinement are in Extended Data Table 1. For discussion purposes, molecule A is used forthwith. CCR9 exhibits the core canonical arrangement of seven transmembrane helices (TM1–TM7) with continuous density observed for all intracellular loops (ICLs) and helix 8 (Fig. 1a). Only extracellular loop 3 was resolved on the extracellular side of the receptor. Additionally, only residual signal is present for the conserved disulfide bridging the top of TM3 (Cys1193.25) and extracellular loop 2. A second disulfide is present in CCR9 linking the N terminus (Cys38) with the top of TM7 (Cys2897.25) as for the related chemokine receptor structures of CCR5/maraviroc11 and CXCR4/IT1t12. Structural superposition of the 7TM core of CCR9 with both CCR5 and CXCR4 (sequence identity 35%, Extended Data Fig. 5) achieves a Cα root mean square deviation of 1.9 Å and 2.5 Å, respectively, with the main differences across the extracellular halves of the receptors (Fig. 1b–g). Compared with CCR5 and CXCR4, the tops of TM3 and TM6 of CCR9 are moved in towards the central axis of the helical bundle, and TM5 is moved outwards, with the differences being greatest between CCR9 and CXCR4. These changes in transmembrane helix position are possibly a consequence of the lack of a small molecule bound in the extracellular portion of the CCR9 transmembrane bundle. Strong and unambiguous density is found for vercirnon on the intracellular side of the receptor contacting TM1, TM2, TM3, TM6, TM7 and helix 8 in an allosteric pocket within the helix bundle open to the cytoplasm (Fig. 2a and Extended Data Fig. 6). So far, the only other structural examples of small molecules binding towards the intracellular side of a receptor to effect allosteric antagonism are provided by the class B structures of corticotropin-releasing factor receptor type 1 (CRF R) in complex with the small-molecule antagonist CP-376395 (ref. 13) and the glucagon receptor (GCGR) in complex with MK-0893 (ref. 14). However, while CP-376395 is found in a pocket approximately 18 Å from the centre of the orthosteric cavity of CRF R, and MK-0893 adopts an extra-helical binding mode towards the bottom of TM6 in GCGR, the position of vercirnon bound to CCR9 is unique in both distance from the orthosteric site (approximately 33 Å) and in occupying a pocket with cytoplasmic access. Moving to the molecular details of the CCR9–StaR–vercirnon interaction, the sulfone group of vercirnon hydrogen bonds with the backbone amino groups of Glu322, Arg323 and Phe324, acting as a helix cap for the N terminus of helix 8 in CCR9. Favourable interactions are also made with the side chain of Tyr3177.53 (of the conserved NP7.50xxY(x) F motif) from above the sulfone group. Mutation of Tyr3177.53, Phe324 and Gly3217.57 to Ala, three highly conserved residues across all chemokine receptors (Fig. 3a, b and Extended Data Table 2), severely decreases vercirnon binding to CCR9 (Fig. 3c and Extended Data Fig. 7), highlighting the importance of these residues in forming the core scaffold of the intracellular allosteric binding site, with Gly3217.57 contributing the necessary conformational flexibility in the junction of TM7–helix-8 to orient the N terminus of helix 8 for ligand interaction. The ligand pyridine-N-oxide group is oriented towards the intracellular face of the receptor at the cytoplasmic entrance to the ligand binding cavity. The pyridine-N-oxide is surrounded by polar residues located on the intracellular extremities of TM2, TM3 and the TM7–helix-8 hinge region including Thr832.39, Asp842.40, Arg1443.50, Arg323 (on helix 8) Thr81 (on ICL1)—the last two being within hydrogen bonding distance of the pyridine-N-oxide (Fig. 2b). Mutation of Thr81 to glutamic acid reduces vercirnon binding compared with wild type (Fig. 3c), presumably as a result of the glutamic-acid side chain no longer being poised to make a polar contact with the ligand and/or fully engaging with Arg323 on helix 8. Finally, the ketone group of vercirnon is engaged in a hydrogen bond with the side chain of Thr2566.37, resulting in a ligand-mediated polar network linking TM6 across to ICL1, TM7 and the junction with helix 8 (Fig. 2b). The tert-butylphenyl group anchors vercirnon in a cavity formed by TM1, TM2, TM7 and helix 8 and is characterized by concurrent lipophilic and hydrophilic residues. The lipophilic tert-butyl group faces towards the TM1–TM2 interface and makes hydrophobic interactions with Val691.53, Val721.56, Tyr731.57 in TM1 and Leu872.43 in TM2. Phe324 (on helix 8) and Tyr3177.53 make edge-to-face π–π stacking with the aromatic core of the tert-butylphenyl group (Fig. 2b). Other favourable hydrophobic interactions occur with the aliphatic portion of Arg323 and the side chain of Leu872.43, which is concomitantly engaged with the chlorophenyl part of the ligand. The chlorophenyl moiety of vercirnon is located in a narrow, apolar cavity surrounded by several hydrophobic residues from TM2, TM3, TM6 and TM7. The chloro group, pointing up towards the central core of the receptor between TM3 and TM6, is located between the residues Leu872.43, Ile1403.46 and Val2596.40. The aromatic part of the chlorophenyl group is located between the hydrophobic surface of Leu872.43 and the main chain of Ala2556.36. Mutation of Leu872.43 to phenylalanine abolishes vercirnon binding to CCR9 (Fig. 3c), probably as a result of filling the cavity between TM2, TM3 and TM6 with a bulky aromatic side chain. The aromatic ring of Tyr3177.53 and the methyl group of Thr832.39 also contribute to favourable interactions with the chlorophenyl ring. The conservative stabilizing mutation V255A is found in the proximity of the chlorophenyl group of vercirnon; however, none of the stabilizing mutations altered vercirnon binding properties of the receptor compared with wild type (see earlier). Molecular dynamics simulations of vercirnon bound to CCR9 (both StaR and wild type) showed stable interactions between the ligand and the residues in the binding site, with hydrogen bonds anchoring the sulfone group to the backbone of Arg323 and Phe324. However, after removal of ligand, molecular dynamics simulations of the pseudo-apo model showed a reorientation of side chains of Tyr3177.53, Arg323 and Phe324 towards the centre of the transmembrane bundle (Extended Data Fig. 8). Interestingly, the corresponding region in the CCR5 (ref. 11) structure is similar to the CCR9 pseudo-apo model after molecular dynamics. Small-molecule chemokine receptor antagonists may be split into two broad chemical classes: tertiary amines and non-amines. Tertiary amines represent most compounds identified so far and probably engage a buried acidic residue (E2837.39 in the CCR5–maraviroc complex11) in the now well-understood class A transmembrane ligand-binding site region, explaining the preponderance of these molecules in chemical literature. Non-amines, such as vercirnon, have been less frequently reported and display pharmacological properties inconsistent with typical receptor antagonism. Interestingly, pepducin ATI-2341, a potent agonist of CXC-type receptor 4 (CXCR4) and whose peptide sequence derives from the first ICL of the receptor, suggests modulation of receptor activity by acting at the intracellular receptor surface15. Furthermore, mutagenesis studies have repeatedly suggested that many of the non-amine class of chemokine antagonists bind near the intracellular surface of receptors, for example the highly CCR4 selective pyrazinyl-sulfonamide series16. For the dual CXCR1/2 squaramide antagonist SCH-527123, mutagenesis of CXCR2 suggests an intracellular allosteric pocket17, 18 lined by Thr832.39, Asp842.40, Tyr3147.53 and Lys3207.59, correlating with the vercirnon binding site in CCR9 (Extended Data Fig. 5); indeed a similar intracellular interaction mode may also exist for SB-656933 (ref. 19) binding to CXCR2. Additionally, investigation of two CXCR2 antagonists exhibiting 1000-fold selectivity over CXCR1, shows that selectivity can be reversed by swapping the receptor C-terminal tails, specifically mapping to residue Lys/Asn7.59 (correlating to Arg3237.59 in CCR9 which makes a direct contact to the pyridine-N-oxide of vercirnon)20. Pharmacological evidence for an intracellular allosteric binding site in CXCR2 is further provided by the insurmountable inhibition of CXCL8-promoted β-arrestin-2 recruitment by SB-265610 (ref. 21). Triazolylpyridylbenzenesulfonamides (CCR2), indazolesulfonamides (CCR4), repertaxin (CXCR1) and dihydroquinazolines (CXCR3) represent additional examples of non-amine chemokine antagonists5. The chemical similarity of several of these compounds to vercirnon, particularly the CCR2 and CCR4 antagonists that contain an aromatic sulfonamide (found capping helix 8 in CCR9), is highly suggestive of analogous sites on the intracellular face of their respective receptors. Overall, a consideration of the chemical nature of non-amine ligand classes, their pharmacological behaviour and evidence from mutagenesis supports the notion that an intracellular binding site may exist in many chemokine receptors, and that subtype-selective ligands can often be identified. Resolution of the structural details of this site in CCR9 facilitates further studies of non-amine chemokine antagonists using structure-based drug design. In response to chemokine binding, CCR9 and chemokine receptor signalling in general have been most widely characterized via the heterotrimeric G-protein G transducer. However, C-terminal receptor phosphorylation by GRK can mediate β-arrestin binding, desensitization and internalization, alongside activation of, for example, Src, PI3K and MAPK22, with vercirnon inhibiting such signalling10. In structural terms, class A receptor agonist binding elicits a rigid-body movement along TM6, altering the interface to TM5 and causing an outward movement of the intracellular half of TM6 alongside an upward movement of TM3 (refs 23, 24). Superposition of CCR9–vercirnon with the β2–AR–G complex structure25 using the core transmembrane bundles provides a structural basis for intracellular allosteric antagonism (Fig. 4a). Assuming that G binds analogously, the G-protein clashes with vercirnon and TM6/ICL3 of CCR9, a likely consequence of vercirnon mediating a network of polar contacts (see earlier) from TM6 across to TM7/helix 8 and ICL1, which holds TM6 inwards towards the receptor’s central helical axis. This, alongside acting as a steric wedge within the helical bundle, restricts the required movements of TM6/TM3, thereby abrogating G-protein binding. Superposition with the structure of rhodopsin bound to arrestin26 demonstrates a similar situation where vercirnon–CCR9 interactions specifically occupy two of the major arrestin-receptor interfaces. Additionally, the junction of TM7–helix-8 in rhodopsin and the finger loop of arrestin directly clash with vercirnon (Fig. 4b). The structure of CCR9 complexed with vercirnon provides the first detailed view of a small molecule bound on the intracellular surface of a G-protein-coupled receptor, in a pocket within the helical bundle of the receptor but open to the cytoplasm. This novel allosteric pocket may be targeted for the design of selective small-molecule antagonists of CCR9 (or related chemokine receptors). Since the intracellular regions of the receptor that interact with G proteins are overlapping but not identical to those that engage β-arrestin, a unique opportunity may now exist to deploy structure-based drug design techniques in fine-tuning molecules that differentially modulate biased signalling cascades and functional outcomes in the chemokine receptor family.


News Article | December 14, 2016
Site: www.nature.com

A ternary complex between an engineered construct of human CCR2 isoform B (further referred to as CCR2-T4L or simply CCR2), an orthosteric antagonist BMS-681 (compound 13d in ref. 6), and an allosteric antagonist CCR2-RA-[R]7 was crystallized using the lipidic cubic phase (LCP) method8, and the structure was determined to 2.8 Å resolution (Extended Data Table 1 and Extended Data Fig. 1). Simultaneous addition of two compounds markedly stabilized detergent-solubilized CCR2-T4L compared with twice the concentration of each compound individually (Fig. 1a), suggesting concurrent binding of CCR2-RA-[R] and BMS-681 to the receptor. The presence of both compounds was critical for crystallization. In the structure, CCR2 adopts the canonical fold of class A G-protein-coupled receptors (GPCRs) with seven transmembrane (TM) helices connected by three extracellular (EC) and three intracellular (IC) loops (Fig. 1b). Both compounds are visible in the electron density (Fig. 1b–d); BMS-681 binds in the extracellular orthosteric pocket (Fig. 1b, c) while CCR2-RA-[R] is located more than 30 Å away (Fig. 1b, d), in a site that is the most intracellular allosteric pocket observed in class A GPCRs so far (Fig. 1e). The binding site of CCR2-RA-[R] spatially overlaps with the G-protein-binding site in homologous receptors (Fig. 1f). As for other chemokine receptors9, 10, 11, 12, CCR2 is expected to have two conserved disulfide bonds in its extracellular domains, with Cys32–Cys277 connecting the amino (N) terminus to ECL3 (NT–ECL3), and Cys113–Cys190 connecting TM3 to ECL2. Electron density is apparent for the ECL2–TM3 disulfide bond but not for the N-terminal residues 1–36 or the NT–ECL3 disulfide bond (Fig. 1b, c). Because the NT–ECL3 disulfide bond has been shown to be important for CCR2 signalling13, its absence is unlikely to be an inherent feature of the receptor; instead, it might be caused by strain of the bond in the ligand-bound state of the receptor14, possibly exacerbated by solvent exposure and radiation damage of the crystals15. As with other chemokine receptors, the extracellular orthosteric pocket of CCR2 can be divided into a major and a minor subpocket, defined by helices III–VII, and helices I–III and VII, respectively, and separated by residues Y1203.32 and E2917.39 (superscript indicates residue number according to Ballesteros–Weinstein nomenclature). BMS-681 binds predominantly in the minor subpocket (Fig. 2a, b) and buries 366.3 Å2 of surface area. The 6-trifluoromethyl quinazoline moiety protrudes between helices I and VII towards the lipid bilayer, while the tri-substituted cyclohexane packs against W982.60. The γ-lactam secondary exocyclic amine forms a hydrogen bond with the hydroxyl of T2927.40, which is critical for binding of chemically related compounds such as BMS-558 (compound 22 in ref. 16) and the Teijin lead series17, 18. This amine is also within hydrogen-bonding distance from the backbone carbonyl of Q2887.36. The carbonyl oxygen of the γ-lactam forms a hydrogen bond with Y491.39, which itself is hydrogen-bonded to the side chain of T2927.40. The N1 nitrogen of the quinazoline is within 4 Å of the Q2887.36 side chain. The protonated tertiary amine on the cyclohexane ring is proximal to a structured water molecule in the binding site. Some CCR2 antagonists, particularly those containing a basic amine, are known to depend on the conserved E2917.39 in the receptor19; however, no direct interaction is observed between E2917.39 and BMS-681. The receptor-bound, bioactive conformation of BMS-681 is strikingly similar to the crystallographic conformation of free BMS-681 (Fig. 2c and Extended Data Table 2), suggesting the absence of internal strain in the bound state. BMS-681 engages several residues that are critical for CCL2 binding and/or activation of CCR2 (refs 17, 18) including Y491.39, W982.60, Y1203.32, and T2927.40. Thus, it seems to directly compete with chemokine binding to the orthosteric pocket. Additionally, by inserting between helices I and VII, BMS-681 may put strain onto residues C32-V37 connecting TM1 to ECL3, destabilize the conserved NT–ECL3 disulfide bond (absent in the structure), and prevent the N terminus and TM1 from adopting a productive chemokine binding conformation observed in homologous receptor–chemokine structures11, 12 (Extended Data Fig. 2). On the opposite side of the receptor, CCR2-RA-[R] is caged by the intracellular ends of helices I–III and VI–VIII and buries 297.8 Å2 of surface area. The inner hydrophobic part of the cage is made by V631.53, L671.57, L812.43, L1343.46, A2416.33, V2446.36, I2456.37, Y3057.53, and F3128.50, while the outer (cytosol-facing) polar part consists of T772.39, R1383.50, G3098.47, K3118.49, and Y3158.53 (Fig. 2d, e), as well as the backbones of engineered R2376.29 and K2406.32. The binding pocket of CCR2-RA-[R] is highly enclosed and possesses a balanced combination of hydrophobic and polar features, all of which favours pocket ‘druggability’5. Owing to the lack of a side-chain on G3098.47, the hydroxyl and pyrrolone carbonyl groups of CCR2-RA-[R] can hydrogen-bond to the exposed backbone amides of E3108.48, K3118.49, and F3128.50 (Fig. 2d, e). The acetyl group of the compound resides near the terminal amine of K3118.49. The critical roles of V2446.36, Y3057.53, K3118.49, and F3128.50 in CCR2-RA-[R] binding were established by an earlier mutagenesis study20. Because homologues of several residues in the CCR2-RA-[R] binding pocket directly couple to the G protein in bovine rhodopsin21 and the β adrenergic receptor (β AR)22 structures (Extended Data Fig. 3), CCR2-RA-[R] appears to sterically interfere with G-protein binding to CCR2. The structure suggests an interesting symmetrical mechanism for the concurrent antagonistic action of the two compounds. BMS-681 interferes with chemokine binding directly and with G-protein coupling indirectly, by stabilizing an inactive, presumably G-protein-incompatible6, conformation of the receptor. Conversely, CCR2-RA-[R] directly prevents G-protein coupling and allosterically inhibits binding of the CCL2 chemokine23, which, like most GPCR agonists, requires an active, G-protein-associated receptor for high affinity binding23. Bi-directional allosteric communication between the extra- and intracellular sides of the receptor is reminiscent of that previously observed in adenosine A receptor (AA R)24 and β AR25 using allosteric inverse agonist antibodies/nanobodies that target the same epitope as CCR2-RA-[R]. Similar to these antibodies, CCR2-RA-[R] was previously shown to allosterically enhance, and to be allosterically enhanced by, binding of orthosteric antagonists23, demonstrating positive binding cooperativity. We further characterized this cooperativity by studying the binding of BMS-681 to wild-type CCR2 and the crystallization construct CCR2-T4L using previously characterized radioactive probes [3H]INCB-3344 (ref. 23) (orthosteric) and [3H]CCR2-RA (allosteric). In equilibrium competition binding assays on wild-type CCR2, both INCB-3344 and CCR2-RA-[R] displaced their homologous radioligand with half-maximum inhibitory concentration (IC ) values of 17 and 13 nM, respectively (Extended Data Fig. 4a, b and Extended Data Table 3), comparable to previously reported values23. Compared to wild-type CCR2, the affinity of both antagonists towards CCR2-T4L was improved by approximately twofold, suggesting a slight engineering-related shift towards the inactive state. BMS-681 fully displaced [3H]INCB-3344 with nanomolar affinities for both constructs, but did not displace [3H]CCR2-RA. Instead, at 1 μM concentration it enhanced the binding of [3H]CCR2-RA by >30% (Extended Data Fig. 4a, b and Extended Data Table 3). In kinetic radioligand experiments, the presence of BMS-681 also increased total binding of [3H]CCR2-RA to both wild-type CCR2 and CCR2-T4L, with the increase as high as 62% in the case of CCR2-T4L (Extended Data Fig. 4c, d and Extended Data Table 4). BMS-681 (1 μM) decreased the dissociation rate constant of [3H]CCR2-RA, while producing a slight increase (wild-type CCR2) or no change (CCR2-T4L) in the observed association rate constants. Moreover, for CCR2-T4L, the presence of BMS-681 changed the biphasic dissociation profile of [3H]CCR2-RA to monophasic, suggesting stabilization of the receptor population in a homogenous conformational state (Extended Data Table 4). Along with the stability and equilibrium binding data, these results further corroborate the hypothesis that BMS-681 and CCR2-RA-[R] cooperatively stabilize a preferred inactive conformation of CCR2-T4L. We next analysed the structure of double-antagonist-bound CCR2-T4L to better understand this conformation. The plethora of existing class A GPCR structures suggests a conserved conformational signature of an active receptor state26. This signature involves increased separation between the intracellular end of helix VI and the rest of the TM bundle, an inward repositioning and rotation of helix VII, and concerted repacking of the highly conserved microswitches R3.50 (of the DR3.50Y motif), Y5.58, and Y7.53 (of the NPxxY7.53 motif) (Fig. 3a, b) to form an intracellular binding interface for G protein. Furthermore, rather than adopting either an ‘on’ or ‘off’ state, receptors can occupy an ensemble of intermediate conformations27. The active state signature is fully represented in US28, the only agonist-bound chemokine receptor crystallized so far12 (Fig. 3a–c). By contrast, the double-antagonist-bound CCR2 structure appears to occupy the opposite end of the activation spectrum as it shares the conformational microswitch signatures of the most inactive GPCR structures observed thus far (Fig. 3a–e). As in the inactive CCR5–maraviroc complex10, the intracellular ends of CCR2 helices III and VI are close together, and the conserved R3.50 interacts with D3.49 and T2.39, effectively disrupting the G-protein-binding pocket (Fig. 3b, d, e). Similarly, in both CCR2 and CCR5 structures, the intracellular end of helix VII is in the inactive outward-facing conformation with Y7.53 pointing towards helix II rather than the centre of the bundle. However, in CCR5, Y5.58 is oriented towards the centre of the bundle, whereas in the present CCR2 structure, it faces the lipid and is sterically blocked from approaching R3.50 and Y7.53 by F6.38 (Fig. 3d, e). The net result of these interactions is that the crystallographically observed conformation of CCR2 appears to be even more inactive than that of CCR5 and most similar to dark rhodopsin28 and Fab-bound β AR29. Although receptor construct engineering appears to contribute to stabilization of this inactive state, the ligand binding and thermal denaturation data suggest that the concerted action of the two antagonists is also important. By directly interacting with the conserved activation microswitch residues, CCR2-RA-[R] is perfectly positioned to stabilize this inactive state: it sterically blocks Y7.53 from populating the active conformation and is propped against R3.50, restricting its orientation away from the G-protein interface (Fig. 3b). Although located 30 Å away, BMS-681 appears to cooperate with CCR2-RA-[R] through their common interactions with helix VII, which moves outwards on the intracellular side (opposite to its movement during activation) and inwards on the extracellular side (relative to CCR5 and US28) (Fig. 3f). The CCR2 structure has general implications for the design of drugs targeting chemokine receptors as a family. As with most protein–protein interfaces, the orthosteric binding pockets of chemokine receptors are large, wide open, and highly polar. Chemokines explore numerous hotspots within these pockets and their binding is additionally reinforced by the interaction with the flexible N termini of the receptors11, 12 (Fig. 4a), collectively making for an extensive and versatile interaction that is conceptually difficult to inhibit with small molecules. The structure of CCR2 with BMS-681 and CCR2-RA-[R] extends the repertoire of ideas that can be used to overcome these obstacles. The binding mode of BMS-681 (Fig. 4b) contrasts with both the binding mode of maraviroc to CCR5 (Fig. 4c) where the ligand spans the major and the minor subpockets of the receptor, and that of IT1t to CXCR4 (Fig. 4d) where the ligand is entirely accommodated in the minor subpocket. While occupying the minor subpocket of CCR2, BMS-681 protrudes between helices I and VII towards the lipid bilayer (Fig. 4b) in an interaction facilitated by the trifluoromethyl group that is often present in CCR2 antagonists30. This interaction enables hydrophobic anchoring of BMS-681 to the otherwise polar and open binding site of CCR2; by doing so, it parallels the role of other unique non-polar subpockets exploited by crystallized small molecule antagonists of CCR5 and CXCR4 (Fig. 4b–d). The novel subpocket explored by BMS-681 may have an additional advantage of disrupting the chemokine-compatible conformation of the receptor N terminus (Extended Data Fig. 2). CCR2-RA-[R] demonstrates a previously unseen binding mode within an allosteric pocket on the intracellular side of CCR2. Although relatively small, this pocket has a desirable balance of polarity and hydrophobicity (Figs 2e, 4e). Homologous pockets may be present in other chemokine receptors, owing to a conserved G8.47; in fact, compound binding in homologous regions has been indirectly demonstrated for CCR1 and CCR5, and directly for CCR4 (ref. 31), CXCR1, and CXCR2 (ref. 32). In most other receptors that have been crystallized thus far, the non-glycine residue at position 8.47 appears to both reduce the pocket volume and block access to the backbone amides of helix 8; consequently, the homologous pockets in these receptors may not be druggable although negative allosteric modulation with antibodies and nanobodies targeting the same region has been reported24, 25. By simultaneously competing with G protein and blocking activation-related conformational changes, compound binding in the allosteric pocket seems a powerful way to antagonize the receptor. Therefore, for receptors in which the allosteric pocket is druggable, targeting it with small molecules may open new avenues for GPCR drug discovery.


News Article | November 21, 2016
Site: www.newsmaker.com.au

Future Market Insights delivers key insights on the global engineering plastics market in an upcoming research publication titled, “Engineering Plastics Market: Global Industry Analysis and Opportunity Assessment, 2016 – 2026”. The global engineering plastics market is projected to register a healthy CAGR of 7.2% in terms of value and 5.7% in terms of volume during the forecast period. Future Market Insights analyses the market performance and provides information on the key factors and trends impacting market growth over the forecast period 2016–2026. The report segments the global engineering plastics market on the basis of Product Type into Polyamides (PA), Polycarbonates (PC), Polyoxymethylene (POM), Polybutylene terephthalate (PBT), Acrylonitrile butadiene styrene (ABS) and Styrene Acrylonitrile (SAN), High Performance Polymers, Fluoropolymers, Polymethyl methacrylate (PMMA), and Others (includes UHMWPE/UHMW, TPI alloys and blends, etc.); and on the basis of Application into Automotive and transportation, Electrical and electronics, Construction, Medical, Industrial and machinery, Packaging, and Others (includes furniture and fixtures, sports goods, leisure products, etc.). The Automotive and transportation segment is increasingly inclined towards adoption of engineering plastics products due to their various thermal and mechanical properties. The fuelling demand for engineering plastics is largely from automotive components such as fasteners and supports for chassis and power trains and body panel lens of head lamps as these parts require higher strength materials. Besides mechanical strength, engineering plastics help in reducing the overall weight of the vehicles. Bio-based engineering plastics that help reduce carbon footprint such as polyamides and polycarbonates are also in high demand. Packaging, electrical and electronics, and consumer goods are lucrative segments for bio-based engineering plastics ranging from stiff to flexible grades. Strong market growth is likely to be observed across high performance plastics such as PEI, PEEK, PSU/PES, PCTF, PVDC, PPSU, LCP, PPS. A growing use of engineering plastics by end user industries, especially automotive, transportation, and medical industries is expected to drive global demand over the forecast period. Rapid urbanisation, infrastructure development, and increased income levels across various end-user segments are other factors likely to boost the growth of the global engineering plastics market. However, high costs of engineering plastics, increasing use of alternative substitutes, and fluctuations in the cost of raw materials are expected to hamper the growth of the global engineering plastics market over the forecast period. Global sales revenue of engineering plastics is expected to witness steady incremental growth during the forecast period. In the product type category, the high performance plastics segment is anticipated to register a healthy CAGR of 9.6% between 2016 and 2026, attributed to an increasing application in the medical industry. In the application category, the electrical and electronics segment is estimated to account for 36% value share of the global engineering plastics market by 2016, followed by the automotive and transportation segment (32.1%) and the construction segment (11.1%). This report also covers trends driving each segment and offers analysis and insights of the potential of the engineering plastics market in specific regions. The APEJ region is expected to exhibit the highest market growth due to an increase in population, income levels, and rapid urbanisation in the region. There is plenty of scope in the APEJ region for manufacturing automobiles, consumer appliances, electronic products, medical devices, industrial, and machineries. The APEJ region is anticipated to register a CAGR of 6.8% between 2016 and 2026 in terms of volume. APEJ is expected to gain substantial market share owing to high demand from India and China, especially in the automotive and electrical and electronics industries. The North America market is expected to register a CAGR of 7.3% during the forecast period, owing to an increasing consumption of engineering plastics in the automotive and transportation industry in the region. In terms of volume, the market share of Western Europe and Japan is expected to decrease substantially over the forecast period, as they are mature markets for engineering plastics. The report also profiles leading players dominating the global engineering plastics market. Arkema Group, Asahi Kasei Corporation, BASF SE, Celanese Corporation, Covestro, DSM N.V, DuPont, Lanxess, LG Chem, Mitsubishi Engineering-Plastics Corporation, Saudi Basic Industries Corporation (SABIC), Solvay SA, Teijin Limited, Toray Industries, and Victrex PLC are some of the top companies operating in the global engineering plastics market.


News Article | February 21, 2017
Site: www.businesswire.com

HONG KONG--(BUSINESS WIRE)--Beijing Gas Blue Sky Holdings Limited (“the Company” or “Beijing Gas Blue Sky”, together with its subsidiaries, the “Group”, HKSE stock code: 6828) is pleased to announce that, Mr. Li Weiqi has been appointed as an executive director of the Company and a vice president of the Group; and Mr. Pang Siu Yin has been appointed as an independent non-executive director of the Company, with immediate effect. Mr. Li Weiqi, aged 42, obtained a Bachelor degree of City Gas Engineering from Beijing Construction Engineering College (now Beijing University of Civil Engineering and Architecture) in 1998. Mr. Li has over 18 years of experience in gas design, strategic planning, infrastructure investment and market development. Prior to joining the Company, Mr. Li served as the deputy manager of planning and development of Beijing Gas Group from 2011 to 2016. Mr. Li also held various positions of designer, consultant, business manager and deputy head of marketing in Beijing Gas and Heating Engineering Design Institute for 11 years. Mr. Pang Siu Yin, aged 57, graduated from the University of Leeds with a bachelor of laws degree, obtained a master of business administration degree from the University of Aston, as well as a postgraduate certificate in laws from the University of Hong Kong respectively. Mr. Pang has been a practising solicitor of the high court of Hong Kong since 1990 and was also admitted as a solicitor in England and Wales in 1997. He is currently a partner of LCP, a firm of solicitors in Hong Kong, with his practice focusing on commercial and litigation. Mr. Pang was appointed as an independent non-executive director of Winto Group (Holdings) Limited (stock code: 8238) on 24 July 2015 and an independent non-executive director of Man Sang Jewellery Holdings Limited (stock code: 1466) on 19 November 2016. Mr. Tommy Cheng, Co-Chairman and Executive Director of the Group states that “We are pleased to invite Mr. Li and Mr. Pang as our Board member. Both of them have extensive experience and achieve outstanding performance in related industry. Prior to joining the Company, Mr. Li developed his career in Beijing Gas Group, which is our single largest shareholder since 2016. We believe that the joining of Mr. Li and Mr. Pang will be definitely beneficial to the Group’s development. We are looking forward to working with them closely to further enhance the level of corporate governance of the Group, as well as to promote the Group's business development in the future.” Beijing Gas Blue Sky Holdings Limited (“Beijing Gas Blue Sky”, HKSE stock code: 6828) is an integrated natural gas provider, distributor and operator, with an emphasis on the midstream and downstream natural gas development. Our natural gas business includes: (i) construction and operation of compressed natural gas (“CNG”) and liquefied natural gas (“LNG”) refueling stations for vehicles; (ii) construction of natural gas pipelines and operation of city gas projects by providing piped gas; (iii) direct supply of LNG to end-users; and (iv) trading and distribution of CNG and LNG. The Group has adapted to the “One Belt One Road” policy, and focus on operating and investing natural gas business. The Group is actively expanding its business development and distribution, as well as continues to gradually expanding the scale of operations. Currently, the Group has business presence in several provinces in Northeast China, East China, Central South China and Southwest China, including Liaoning Province, Shandong Province, Anhui Province, Zhejiang Province, Hubei Province, Guizhou Province, Sichuan Province and Hainan Province, etc. In the future, The Group is committed to its vision "develop clean energy, enhance customer value, create a beautiful blue sky". It will continue to actively investing and developing natural gas business, as well as participating in the development of natural gas industry value chain.


News Article | December 19, 2016
Site: www.prnewswire.co.uk

The report "High Performance Plastics Market by Type (Fluoropolymers, High Performance Polyamide, PPS, SP, LCP, AKP, and PI), End-Use Industry (Transportation, Electrical and Electronics, Medical, Industrial), And Region - Global Forecast to 2026", published by MarketsandMarkets, the market size is estimated to grow from USD 14.49 Billion in 2016 to USD 35.27 Billion by 2026, at a CAGR of 9.3% from 2016 to 2026. http://www.marketsandmarkets.com/Market-Reports/high-performance-plastic-market-130930168.html Early buyers will receive 10% customization on this report. The market is driven by the increased usage of high performance plastics materials instead of conventional materials in high temperature applications. Asia-Pacific is currently the largest market for high performance plastics due to increasing demand from emerging countries such as India and China. China is the largest market for high performance plastics in the Asia-Pacific region. Forces driving the market for high performance plastics in Asia-Pacific are: Transportation: The largest end-use industry of the high performance plastics market High performance plastics are used in various end-use industries such as electrical & electronics, medical, transportation, industrial, and others. These are the main end-use industries considered in the report. The transportation segment is estimated to account for the largest share, in terms of value as well as volume, followed by electrical & electronics, in 2016. The medical industry is estimated to grow at the highest CAGR from 2016 to 2026, in terms of value, among all the industries considered. Fluoropolymers: The largest type segment of the high performance plastics market The fluoropolymers type is estimated to account for the largest market share, in terms of value as well as volume, followed by high performance polyamide in 2016. The aromatic ketone polymers segment is estimated to grow at the highest CAGR from 2016 to 2026, in terms of value. The key players in the High Performance Plastics Market are BASF SE (Germany), Daikin Industries, Ltd. (Japan), Celanese Corporation (U.S.), Solvay S.A. (Belgium), Arkema SA (France), Evonik Industries AG (Germany), Kuraray Co., Ltd. (Japan), E. I. duPont de Nemours and Company (U.S.), SABIC (Saudi Arabia) , Victrex Plc (U.K.), and others Medical Plastics Market by Type (PVC, PP, Engg Plastics, PE, PS, Silicones & Others), by Application (Implants, Disposables, Drug delivery devices, Syringes, Diagnostic instruments, Surgical instruments, Catheters, & Others) and by Region - Forecast to 2020 http://www.marketsandmarkets.com/Market-Reports/medical-plastics-market-83738633.html MarketsandMarkets is the largest market research firm worldwide in terms of annually published premium market research reports. Serving 1700 global fortune enterprises with more than 1200 premium studies in a year, M&M is catering to a multitude of clients across 8 different industrial verticals. We specialize in consulting assignments and business research across high growth markets, cutting edge technologies and newer applications. Our 850 fulltime analyst and SMEs at MarketsandMarkets are tracking global high growth markets following the "Growth Engagement Model - GEM". The GEM aims at proactive collaboration with the clients to identify new opportunities, identify most important customers, write "Attack, avoid and defend" strategies, identify sources of incremental revenues for both the company and its competitors. M&M's flagship competitive intelligence and market research platform, "RT" connects over 200,000 markets and entire value chains for deeper understanding of the unmet insights along with market sizing and forecasts of niche markets. The new included chapters on Methodology and Benchmarking presented with high quality analytical infographics in our reports gives complete visibility of how the numbers have been arrived and defend the accuracy of the numbers. We at MarketsandMarkets are inspired to help our clients grow by providing apt business insight with our huge market intelligence repository. Visit MarketsandMarkets Blog @ http://www.marketsandmarketsblog.com/market-reports/chemical Connect with us on LinkedIn @ http://www.linkedin.com/company/marketsandmarkets


News Article | December 19, 2016
Site: www.prnewswire.com

PUNE, India, December 19, 2016 /PRNewswire/ -- The report "High Performance Plastics Market by Type (Fluoropolymers, High Performance Polyamide, PPS, SP, LCP, AKP, and PI), End-Use Industry (Transportation, Electrical and Electronics, Medical, Industrial), And Region - Global Forecast...


News Article | February 24, 2017
Site: www.prnewswire.co.uk

The report "PEEK Market by Type (Glass Filled, Carbon Filled, Unfilled), End User (Electrical & Electronics, Aerospace, Automotive, Oil & Gas, Medical), Region (Europe, North America, Asia-Pacific, Middle East, South America, Africa) - Global Forecast to 2021", published by MarketsandMarkets, The global market is projected to reach USD 664.3 Million by 2021, at a CAGR of 6.3% from 2016 to 2021. Browse 114 market data Tables and 40 Figures spread through 156 Pages and in-depth TOC on "PEEK Market" http://www.marketsandmarkets.com/Market-Reports/polyether-ether-ketone-market-928.html Early buyers will receive 10% customization on this report. The global PEEK market is driven by the strong growth in the demand for light weight high performance materials across various end-use sectors, especially electrical & electronics, aerospace, automotive, oil & gas, and medical. Advancements in terms of product innovations and technologies in the market are also expected to create strong investment opportunities for global players. Ask for PDF of the Report at http://www.marketsandmarkets.com/pdfdownload.asp?id=928 Electrical & electronics is the largest end user segment of the global PEEK market Based on end users, the PEEK market has been segmented into electrical & electronics, aerospace, automotive, oil & gas, medical, and others. The electrical & electronics segment accounted for the largest share of the PEEK market in 2015; and is projected to be the fastest-growing segment from 2016 to 2021. PEEK has various applications in the electrical & electronics industry, including electrical connectors, cable sheaths, computer machinery, transformers, and so on. Glass filled was the largest type segment of the PEEK market Based on type, the PEEK Market has been segmented into glass filled, carbon filled, and unfilled. Glass filled is the most common PEEK type and is projected to grow at the highest CAGR during the forecast period. It is widely used in the electrical & electronics, and transportation (aerospace and automotive) industries. The Asia-Pacific is the fastest growing market for PEEK from 2016 to 2021 The Asia-Pacific region is emerging as the leading consumer of PEEK due to the increasing demand from domestic markets. Increasing applications of PEEK in the electrical & electronics, aerospace, and automotive applications are expected to bring new opportunities to the market. In addition, countries such as China and South Korea are known as the major hubs for the production of electronic components. Moreover, the high economic growth rate, growing manufacturing industries, cheap labor, the growing electronics market, and the global shift of consumption and production capacities from the developed markets to emerging markets are a few factors leading to the growth in demand for PEEK in the Asia-Pacific region. The key players operational in the PEEK market include Victrex plc (U.K.), Solvay S.A. (Belgium), Evonik Industries AG (Germany), and Panjin Zhongrun High Performance Polymers Co. Ltd., (China), among others. High Performance Plastics Market by Type (Fluoropolymers, High Performance Polyamide, PPS, SP, LCP, AKP, and PI), End-Use Industry (Transportation, Electrical and Electronics, Medical, Industrial), and Region - Global Forecast to 2026 http://www.marketsandmarkets.com/Market-Reports/high-performance-plastic-market-130930168.html MarketsandMarkets is the largest market research firm worldwide in terms of annually published premium market research reports. Serving 1700 global fortune enterprises with more than 1200 premium studies in a year, M&M is catering to a multitude of clients across 8 different industrial verticals. We specialize in consulting assignments and business research across high growth markets, cutting edge technologies and newer applications. Our 850 fulltime analyst and SMEs at MarketsandMarkets are tracking global high growth markets following the "Growth Engagement Model - GEM". The GEM aims at proactive collaboration with the clients to identify new opportunities, identify most important customers, write "Attack, avoid and defend" strategies, identify sources of incremental revenues for both the company and its competitors. M&M's flagship competitive intelligence and market research platform, "RT" connects over 200,000 markets and entire value chains for deeper understanding of the unmet insights along with market sizing and forecasts of niche markets. The new included chapters on Methodology and Benchmarking presented with high quality analytical infographics in our reports gives complete visibility of how the numbers have been arrived and defend the accuracy of the numbers. We at MarketsandMarkets are inspired to help our clients grow by providing apt business insight with our huge market intelligence repository. Visit MarketsandMarkets Blog @ http://www.marketsandmarketsblog.com/market-reports/chemical Connect with us on LinkedIn @ http://www.linkedin.com/company/marketsandmarkets


News Article | October 17, 2016
Site: www.theguardian.com

Billionaires are shunning the London luxury property market, with sales of “super prime” £10m-plus homes in the capital collapsing by 86% over the past year. Just five properties were sold for more than £10m in the three months to August 2016, according to an analysis of Land Registry data, compared with 35 in the same period a year earlier. Outside of London, not a single property was sold for more than £10m, compared with ten last year. The average price paid also fell steeply, from £22m to £16.3m, said property group London Central Portfolio, which carried out the analysis. It blamed increasing property taxes, such as the sharp hike in stamp duty and new obligations on non-dom foreign buyers, rather than Brexit, for the decline in prices and activity. Worried developers are now scaling down the most opulent projects, with one newbuild Mayfair block reworked to provide more, smaller, flats in a bid to find buyers. Newbuild sales have slumped in particular, said LCP, which runs investment funds of high-end central London apartments. No super-prime newbuild units were sold over the three-month period, compared with last year where they made up 23% of sales. Naomi Heaton of LCP said: “A price correction was inevitable and is widely reflected in reports of price discounting. Whilst the long term outlook remains compelling, the luxury market is likely to experience continued instability especially in the face of the forthcoming ‘look through’ non-dom inheritance tax ... it may take some years before growth returns.” Many will cheer any downturn in the London property market after years in which price rises have far outstripped local incomes, even of the well-off. Separate research by estate agents Jackson-Stops & Staff has found that homes for sale at less than £100,000 are now extinct in the capital, and suggests that this year homes under £120,000 will completely vanish. But Heaton said the slowdown in the luxury property market should be “very concerning” for the Treasury as it would lead to a decline in stamp duty receipts. She estimated that the reduction in super-prime activity in the last three months alone meant the government could face a £45m fall in stamp duty receipts. The government’s haul from stamp duty, particularly in London, has soared over the past year, but Heaton said that may now hit the buffers. The sudden disappearance of super-rich buyers is forcing developers to reconsider their plans. “Many are looking to divide large, high-priced property into smaller flats to increase their attractiveness. Clivedale, for example, is reworking its flagship Hanover Square development to create four times more units, whilst the green light has been given to Citygrove Securities and McClaren Properties to replace seven Chelsea townhouses with smaller units,” said LCP. Rents are also falling, partly as sellers unable to find buyers choose to rent out their properties instead. Separate data from upmarket property agents Knight Frank found that rents in prime central London locations fell by 4.7% in the year to September, although the number of tenancies agreed reached a record high. But it said the sales market had not fallen as steeply as the LCP figures suggest. It found that price falls were 2.1% in the year to September, noting that the amount of time it took for a property to sell was 14% higher than at the start of the year. Sterling’s 20% devaluation since the EU referendum may bring foreign buyers back into the luxury London market. According to Juwai, which claims to be the biggest international property website for Chinese investors, inquiries were up 12% in August to a record high as the yuan-rich scout around for bargain buys in London. “Ironically, the rapid devaluation of sterling, now attracting foreign investors back to London, may be the biggest hope of salvaging a potentially embarrassing and costly situation,” said Heaton. But the chances of normal people picking up a bargain is remote. The single most expensive residential property sold in the UK during the past three months still went for £25m despite the slowdown – and even then it was a “fixer-upper” requiring total renovation. The six-storey house, 112 Eaton Square, went for just £1.5m less than its £26.5m asking price. The property, famous as the location where a group of rebel Tory MPs plotted to topple wartime prime minister Neville Chamberlain, has been empty for 20 years and the buyer will have spend millions on a restoration.


News Article | March 2, 2017
Site: news.yahoo.com

FILE - In this Feb. 23, 2017 file photo, Marine Le Pen, the French far-right presidential candidate adjuts her hair as she attends a debate in Paris. The European Parliament has voted Thursday March 2, 2017 to lift Le Pen's immunity from prosecution. (AP Photo/Francois Mori) PARIS (AP) — The European Parliament voted Thursday to lift the immunity from prosecution for French far-right leader Marine Le Pen for tweeting gruesome images of Islamic State violence, a crime that carries up to three years in prison in France. The legislature voted by a broad majority in Brussels to clear the way for the possible prosecution of Le Pen over tweets she made in December 2015 showing executions, including the killing of American reporter James Foley by Islamic State extremists. French prosecutors in the city of Nanterre had asked lawmakers to lift the immunity that Le Pen enjoys as a member of the European Parliament. Le Pen, a leading candidate in this year's French presidential election, posted her tweets in response to a journalist who drew an analogy between her anti-immigration National Front party and IS extremists. She was trying to show the difference between the two groups but the effort backfired, drawing widespread condemnation. Le Pen took down the tweet showing the killing of Foley after his family protested, but left up another image of violence by Islamic State extremists. Under French law, publishing violent images can be punished by up to three years in jail and a fine of 75,000 euros ($78,800). Before the vote, Le Pen on Thursday defended her tweets, saying she just wanted to condemn the barbaric practices of IS, also known as Daesh. "I'm a lawmaker. I'm in my role when I condemn Daesh, this is my role," she told French TV station LCP. "And if I don't fulfill my role, I'm worth nothing as a lawmaker. Nobody can prevent a republic's representative from condemning Daesh's acts of violence." Her campaign manager, David Rachline, denounced the lawmakers' actions. The EU parliament decision "marks the difference between those who denounce and fight Islamist fundamentalism and those who want to hide the atrocities," Rachline said. The lifting of Le Pen's immunity does not relate to another corruption case centered on her aide at the European Parliament, who is suspected of being paid from EU money while working on her party's behalf. Le Pen's chief of staff, Catherine Griset, was handed a preliminary charge of receiving money through a breach of trust. The campaign to replace France's unpopular Socialist President Francois Hollande has also been rocked by corruption allegations targeting another top contender, conservative candidate Francois Fillon. Fillon, a former prime minister and once the front-runner in France's two-round April-May presidential election, announced Wednesday that he was summoned to appear before judges on March 15 for allegedly using taxpayers' money to pay family members for jobs that may not have existed. Fillon, however, vowed to stay in the race. Fillon's troubles have benefited centrist independent candidate Emmanuel Macron, who on Thursday announced his policy platform, including boosting European unity and combating populism and corruption. To counter the growing political scandals, Macron said he wants to shrink the size of parliament, introduce term limits and ban officials from hiring family members. He wants to continue good security cooperation with the U.S. despite his ideological differences with Donald Trump. Macron on Thursday called Trump's skepticism toward the Paris Agreement to fight global warming "a deep mistake" and expressed opposition to Trump's proposed U.S. protectionist trade measures. Macron said he would not comment on Le Pen's situation, then added "fortunately our national and European institutions are not losing their common sense." The top two vote-getters in France's April 23 presidential ballot move on to compete in the May 7 presidential runoff. Others in the running include Socialist Benoit Hamon and far-left candidate Jean-Luc Melenchon.


News Article | August 25, 2016
Site: www.spie.org

Optically anisotropic liquid crystal polymer layers are used in each resonant cavity of a resonator array to achieve image selection by polarization for low-cost security labels. The prevalence of counterfeited and pirated goods in modern society means that the demand for novel anti-counterfeiting technologies has become tremendous in recent years. Indeed, the global trade of such items in 2015 was estimated to be worth $960 billion, and a danger to 2.5 million jobs.1 These activities, therefore, place an enormous drain on the global economy. Under these circumstances, much effort has been made in the development of smart security labels for anti-counterfeiting applications. In contrast to conventional labels, these smart security labels are designed to hide information in normal conditions and reveal it in specific viewing conditions. Such viewing conditions arise under specific viewing angles2 and polarization states,3 or upon application of external stimuli (e.g., an electric field, a magnetic field,4 or mechanical stress5). In the development of such security labels, a number of strategies—based on colloidal photonic crystals,6 fluorescent nanostructures,7 and plasmonic nanostructures8—have so far been demonstrated. In these approaches, the manufacturing process relies primarily on the precise manipulation of nanostructures. However, this significantly limits the scalability and throughput of the manufacturing for practical applications. Moreover, the authentication process is rather complicated, and it requires high-cost and high-resolution facilities. It remains a challenge, therefore, to develop a new type of smart security label that can be recognized with the naked eye and that can be fabricated with a scalable and high-throughput process. In this work,9 we demonstrate an array of Fabry-Perot (FP) resonators as a novel and practical route toward the production of highly efficient and low-cost security labels. In these arrays, we incorporate a liquid crystal polymer (LCP) layer inside each resonant cavity (RC), as illustrated in Figure 1(a). The optical anisotropy of this LCP layer means that the FP resonators behave as bandpass filters,10 with different peaks of transmittance for two orthogonal polarizations. To record predefined images, we use a photoalignment process to align the LCP molecules in the FP resonator array along different directions that correspond to the image. Depending on the polarization state of the incident white light, we obtain different images (because of the match/mismatch between the effective refractive indices in different image regions). This unique image selection capability therefore provides an ideal platform for anti-counterfeiting applications. The optical transmittance of our FP resonator for two orthogonal polarizations (one parallel and one perpendicular to the LCP alignment) is shown in Figure 1(b). For these measurements, we used an LCP layer and a photoalignment layer that were 603 and 80nm thick, respectively. The results clearly show that we obtained three resonant peaks (at the 5th, 6th, and 7th orders). In addition, we measured a peak transmittance of about 50%. This is significantly higher than that which is achieved with previous approaches for similar devices. In addition, we find that the peak shift, which results from the difference in refractive index (n ) for the two orthogonal polarizations, was about 40nm. To demonstrate the success of our technique, we constructed an array of our anisotropic elemental FP resonators. We then encoded predefined images onto the array so that only one specific image among them was readable, according to the polarization state of the incident light. To do this—see Figure 2(a)—we used a series of photoalignment processes, in which UV light was polarized along three different directions, to record two images (of ‘SNU’ and ‘MIPD’) on the background of the FP resonator array. In particular, we note that the three polarization states were separated equally by an angle of 60°. Our microscope images of the FP resonators indicate that under unpolarized light—see Figure 2(b)—no image appeared because the n of the different regions were identical. In contrast, when we illuminated the resonators with the same polarization of incident light that we used for the image recordings, we successfully observed—see Figure 2(c) and (d)—the encoded images. In addition, at the mid-angle between the two polarization states, the SNU and MIPD images—see Figure 2(e)—appeared simultaneously (because a linear combination of the two polarization states occurs at the mid-angle between them). These results therefore illustrate that our approach provides a simple scheme for selecting a specific image and for differentiating information with the naked eye, and without a complicated design or fabrication method. In summary, we have demonstrated that an array of FP resonators containing an LCP layer in each RC can be used to achieve image selection according to the polarization state of the incident light. To record different images in the array, we use a series of photoalignment processes to align the LCP molecules in the RCs along different directions, in a massively parallel manner, and over a large area. With our approach, a specific image can only be observed when the input polarization coincides with the polarization state of the recorded image. Our LCP-based FP resonator therefore represents a versatile way of producing low-cost security labels for anti-counterfeiting applications. In our future work we will extend our technology to realize a new type of storage media for multiple holographic images and a platform for visual arts. This work was partly supported through the 2016 BK21 Plus Program of Korea.

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