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Jones S.,University of Glasgow | Asokanathan C.,UK National Institute for Biological Standards and Control | Kmiec D.,UK National Institute for Biological Standards and Control | Irvine J.,University of Glasgow | And 6 more authors.
Vaccine | Year: 2014

Protein-coated microcrystals (PCMCs) were investigated as potential vaccine formulations for a range of model antigens. Presentation of antigens as PCMCs increased the antigen-specific IgG responses for all antigens tested, compared to soluble antigens. When compared to conventional aluminium-adjuvanted formulations, PCMCs modified with calcium phosphate (CaP) showed enhanced antigen-specific IgG responses and a decreased antigen-specific IgG1:IgG2a ratio, indicating the induction of a more balanced Th1/Th2 response. The rate of antigen release from CaP PCMCs, in vitro, decreased strongly with increasing CaP loading but their immunogenicity in vivo was not significantly different, suggesting the adjuvanticity was not due to a depot effect. Notably, it was found that CaP modification enhanced the phagocytosis of fluorescent antigen-PCMC particles by J774.2 murine monocyte/macrophage cells compared to soluble antigen or soluble PCMCs. Thus, CaP PCMCs may provide an alternative to conventional aluminium-based acellular vaccines to provide a more balanced Th1/Th2 immune response. © 2014 The Authors.

Nelson D.J.,University of St. Andrews | Queval P.,National Graduate School of Chemistry, Rennes | Rouen M.,National Graduate School of Chemistry, Rennes | Magrez M.,National Graduate School of Chemistry, Rennes | And 8 more authors.
ACS Catalysis | Year: 2013

Synergic effects between ancillary N-heterocyclic carbenes [(1,3-bis(2,4,6-trimethylphenyl)-1,3-imidazoline-2-ylidene or 1,3-bis(2,6-diisopropylphenyl)-1,3-imidazoline-2-ylidene] and chelating benzylidene-ether ligands were investigated by studying initiation rates and kinetic profiles of Hoveyda-Grubbs (HG) type Ru complexes. A newly designed Ru-benzylidene-oxazinone precatalyst 4 was compared with Grela and Blechert complexes bearing modified isopropyloxy chelating leaving groups and with the standard HG complex to understand how the ancillary and the leaving ligands interact and influence the catalytic activity. © 2013 American Chemical Society.

Hillier I.H.,University of Manchester | Pandian S.,University of Manchester | Percy J.M.,WestCHEM | Vincent M.A.,University of Manchester
Dalton Transactions | Year: 2011

The potential energy surfaces for ring-closing metathesis reactions of a series of simple α,ω-dienes which lead to 5-10 membered ring products, have been explored using density functional theory methods. We have investigated both the conformational aspects of the hydrocarbon chain during the course of the reactions, as well as the stationary structures on the corresponding potential energy surfaces. Extensive conformational searches reveal that the reaction proceeds via the conformation that would be expected for the cycloalkene product, though most unexpectedly, cyclohexene forms via complexes in boat-like conformations. The M06-L density functional has been used to map out the potential energy surfaces, and has identified metallocyclobutane fragmentation as being generally the highest barrier along the pathway. The structural variations along the pathway have been discussed for the reactant hydrocarbons of differing chain length to identify points at which cyclisation events may begin to affect reaction rates. Our study provides an excellent starting point from which to begin to learn about the way RCM reaction outcomes are controlled by diene structure. © 2011 The Royal Society of Chemistry.

Pappas C.G.,WestCHEM | Pappas C.G.,City University of New York | Mutasa T.,University of Strathclyde | Frederix P.W.J.M.,WestCHEM | And 8 more authors.
Materials Horizons | Year: 2015

Ultrasound, i.e. high frequency oscillating pressure waves, is commonly used to overcome kinetic barriers associated with dissolution, assembly and gelation. We demonstrate that ultrasound energy may also be used to achieve transient reorganization of supramolecular nanostructures, which revert back to the original state when sound is switched off. Aromatic peptide amphiphiles, Fmoc-FL and -YL were used to study the transient acoustic response. These systems showed temporary supramolecular transitions that were sequence dependent. The changes observed were due to an altered balance between H-bonding and π-stacking, giving rise in changes in chiral organisation of peptide building blocks. Transient reconfiguration was visualized by TEM and changes in supramolecular interactions characterized by fluorescence, FT-IR and CD. Remarkably, significant differences are observed when compared to thermal heating, which relates to the oscillating and directional characteristics of ultrasound when delivering heat to a system. © The Royal Society of Chemistry.

Zelzer M.,WestCHEM | Zelzer M.,TU Eindhoven | Todd S.J.,Renephra Ltd. | Hirst A.R.,University of Leeds | And 2 more authors.
Biomaterials Science | Year: 2013

Enzyme responsive materials (ERMs) are a class of stimuli responsive materials with broad application potential in biological settings. This review highlights current and potential future design strategies for ERMs and provides an overview of the present state of the art in the area. © 2013 The Royal Society of Chemistry.

Bennie L.S.,WestCHEM | Kerr W.J.,WestCHEM | Middleditch M.,WestCHEM | Watson A.J.B.,WestCHEM
Chemical Communications | Year: 2011

A novel chiral magnesium bisamide has enabled the development of effective asymmetric deprotonation protocols at substantially more elevated temperatures. This new, structurally simple, C 2-symmetric magnesium complex displays excellent levels of asymmetric efficiency and energy reduction in the synthesis of enantioenriched enol silanes. © 2011 The Royal Society of Chemistry.

Pappas C.G.,WestCHEM | Abul-Haija Y.M.,WestCHEM | Flack A.,WestCHEM | Frederix P.W.,WestCHEM | Ulijn R.V.,WestCHEM
Chemical communications (Cambridge, England) | Year: 2014

Supramolecular structures were produced by in situ enzymatic condensation of Fmoc-Phe-(4-X), where X denotes electron withdrawing or donating groups, with Phe-NH2. The relative contribution of π-stacking and H-bonding interactions can be regulated by the nature of X, resulting in tuneable nanoscale morphologies.

Sahoo J.K.,WestCHEM | Nalluri S.K.M.,WestCHEM | Javid N.,WestCHEM | Webb H.,WestCHEM | Ulijn R.V.,WestCHEM
Chemical Communications | Year: 2014

We report on a supramolecular self-assembly system that displays coupled light switching, biocatalytic condensation/hydrolysis and gelation. The equilibrium state of this system can be regulated by light, favouring in situ formation, by protease catalysed peptide synthesis, of self-assembling trans-Azo-YF-NH2 in ambient light; however, irradiation with UV light gives rise to the cis-isomer, which readily hydrolyzes to its amino acid derivatives (cis-Azo-Y + F-NH2) with consequent gel dissolution. This journal is © the Partner Organisations 2014.

PubMed | WestCHEM
Type: Journal Article | Journal: Chemical communications (Cambridge, England) | Year: 2011

A novel chiral magnesium bisamide has enabled the development of effective asymmetric deprotonation protocols at substantially more elevated temperatures. This new, structurally simple, C(2)-symmetric magnesium complex displays excellent levels of asymmetric efficiency and energy reduction in the synthesis of enantioenriched enol silanes.

PubMed | University of Southampton, University of Glasgow, University of Nottingham and WestCHEM
Type: Journal Article | Journal: ACS nano | Year: 2016

Out of their niche environment, adult stem cells, such as mesenchymal stem cells (MSCs), spontaneously differentiate. This makes both studying these important regenerative cells and growing large numbers of stem cells for clinical use challenging. Traditional cell culture techniques have fallen short of meeting this challenge, but materials science offers hope. In this study, we have used emerging rules of managing adhesion/cytoskeletal balance to prolong MSC cultures by fabricating controllable nanoscale cell interfaces using immobilized peptides that may be enzymatically activated to change their function. The surfaces can be altered (activated) at will to tip adhesion/cytoskeletal balance and initiate differentiation, hence better informing biological mechanisms of stem cell growth. Tools that are able to investigate the stem cell phenotype are important. While large phenotypical differences, such as the difference between an adipocyte and an osteoblast, are now better understood, the far more subtle differences between fibroblasts and MSCs are much harder to dissect. The development of technologies able to dynamically navigate small differences in adhesion are critical in the race to provide regenerative strategies using stem cells.

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