Japan Biological Informatics Consortium JBiC

Tokyo, Japan

Japan Biological Informatics Consortium JBiC

Tokyo, Japan
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Takagi M.,Japan Biological Informatics Consortium JBIC | Shin-Ya K.,Japan National Institute of Advanced Industrial Science and Technology
Journal of Antibiotics | Year: 2012

To construct a natural product library for drug screening, we isolated secondary metabolites from a wide variety of actinomycetes cultured from marine sponges. The results suggested that marine sponges are a promising source of actinomycetes with the potential to produce new metabolites. Furthermore, we evaluated the chemical space occupied by our natural product library (CB library) by multidimensional principal component analysis and compared it with a commercially available compound library (ZINC library), which was randomly selected from the ZINC library (approximately 30 000 000 compounds). The CB library occupied a wider chemical space than the ZINC library. Bioactive compounds in the CB library possessed a wide chemical space that was not covered by ZINC library. These results indicate that the CB library mainly comprises secondary metabolites from actinomycetes, and it has great potential as a source of compounds for drug screening. © 2012 Japan Antibiotics Research Association.

Fuse S.,Tokyo Institute of Technology | Okada K.,Tokyo Institute of Technology | Iijima Y.,Tokyo Institute of Technology | Munakata A.,Japan Biological Informatics Consortium JBIC | And 5 more authors.
Organic and Biomolecular Chemistry | Year: 2011

The total synthesis of a natural product HDAC inhibitor, spiruchostatin B, was successfully achieved. A 5-step synthesis that included an asymmetric aldol reaction was carried out in an automated synthesizer to provide an (E)-(S)-3-hydroxy-7-thio-4-heptenoic acid segment that is the crucial structure of cysteine-containing, depsipeptidic natural products such as spiruchostatins, FK228, FR901375, and largazole for their inhibitory activity against HDACs. © 2011 The Royal Society of Chemistry.

Doi T.,Tohoku University | Shibata K.,Tokyo Institute of Technology | Yoshida M.,Tohoku University | Takagi M.,Japan Biological Informatics Consortium JBIC | And 4 more authors.
Organic and Biomolecular Chemistry | Year: 2011

Total synthesis of the (S)-stereoisomer of telomestatin (1) was accomplished. (S)-Telomestatin exhibited potency four times that of the natural product, (R)-telomestatin, which was the most potent telomerase inhibitor previously reported. In the circular dichroism spectral analysis of the complexes possessing randomly structured single-stranded d[TTAGGG]4 oligonucleotide, (S)-telomestatin, like (R)-telomestatin, induced an antiparallel G-quadruplex structure. The melting temperature (Tm) value of the (S)-isomer complex was greater than that of the (R)-telomestatin complex. Therefore, it is concluded that the stereochemistry of the thiazoline of telomestatin is important to the binding ability of a G-quadruplex binder, and (S)-telomestatin as a G-quadruplex binder is more potent than the natural product. © 2011 The Royal Society of Chemistry.

Healy A.R.,University of St. Andrews | Izumikawa M.,Japan Biological Informatics Consortium JBIC | Slawin A.M.Z.,University of St. Andrews | Shin-Ya K.,Japan National Institute of Advanced Industrial Science and Technology | Westwood N.J.,University of St. Andrews
Angewandte Chemie - International Edition | Year: 2015

Recent reports have highlighted the biological activity associated with a subfamily of the tetramic acid class of natural products. Despite the fact that members of this subfamily act as protein-protein interaction inhibitors that are of relevance to proteasome assembly, no synthetic work has been reported. This may be due to the fact that this subfamily contains an unnatural 4,4-disubstitued glutamic acid, the synthesis of which provides a key challenge. A highly stereoselective route to a masked form of this unnatural amino acid now enabled the synthesis of two of the possible diastereomers of JBIR-22 and allowed the assignment of its relative and absolute stereochemistry. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mashimo T.,Japan Biological Informatics Consortium JBIC | Mashimo T.,Information and Mathematical Science Bio Inc. | Fukunishi Y.,Japan National Institute of Advanced Industrial Science and Technology | Kamiya N.,Osaka University | And 5 more authors.
Journal of Chemical Theory and Computation | Year: 2013

A molecular dynamics (MD) simulation program for biological macromolecules was implemented with a non-Ewald scheme for long-ranged electrostatic interactions and run on a general purpose graphics processing unit (GPU). We recently developed several non-Ewald methods to compute the electrostatic energies with high precision. In particular, the zero-dipole summation (ZD) method, which takes into account the neutralities of charges and dipoles in a truncated subset, enables the calculation of electrostatic interactions with high accuracy and low computational cost, and its algorithm is simple enough to be implemented in a GPU. We developed an MD program with the space decomposition algorithm, myPresto/psygene, and applied it to several biological macromolecular systems with GPUs implementing the ZD method. Rapid computing performance with high accuracy was obtained. © 2013 American Chemical Society.

Muraoka N.,Keio University | Yamakawa H.,Keio University | Miyamoto K.,Keio University | Sadahiro T.,Keio University | And 19 more authors.
EMBO Journal | Year: 2014

Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors or microRNAs. However, induction of functional cardiomyocytes is inefficient, and molecular mechanisms of direct reprogramming remain undefined. Here, we demonstrate that addition of miR-133a (miR-133) to Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Mesp1 and Myocd improved cardiac reprogramming from mouse or human fibroblasts by directly repressing Snai1, a master regulator of epithelial-to-mesenchymal transition. MiR-133 overexpression with GMT generated sevenfold more beating iCMs from mouse embryonic fibroblasts and shortened the duration to induce beating cells from 30 to 10 days, compared to GMT alone. Snai1 knockdown suppressed fibroblast genes, upregulated cardiac gene expression, and induced more contracting iCMs with GMT transduction, recapitulating the effects of miR-133 overexpression. In contrast, overexpression of Snai1 in GMT/miR-133-transduced cells maintained fibroblast signatures and inhibited generation of beating iCMs. MiR-133-mediated Snai1 repression was also critical for cardiac reprogramming in adult mouse and human cardiac fibroblasts. Thus, silencing fibroblast signatures, mediated by miR-133/Snai1, is a key molecular roadblock during cardiac reprogramming.

Okada Y.,Keio University | Sato K.,Japan Biological Informatics Consortium JBIC | Sakakibara Y.,Keio University
Pacific Symposium on Biocomputing 2010, PSB 2010 | Year: 2010

RNAz, a support vector machine (SVM) approach for identifying functional non-coding RNAs (ncRNAs), has been proven to be one of the most accurate tools for this goal. Among the measurements used in RNAz, the Structure Conservation Index (SCI) which evaluates the evolutionary conservation of RNA secondary structures in terms of folding energies, has been reported to have an extremely high discrimination capability. However, for practical use of RNAz on the genome-wide search, a relatively high false discovery rate has unfortunately been estimated. It is conceivable that multiple alignments produced by a standard aligner that does not consider any secondary structures are not suitable for identifying ncRNAs in some cases and incur high false discovery rate. In this study, we propose C-SCI, an improved measurement based on the SCI applying γ-centroid estimators to incorporate the robustness against low quality multiple alignments. Our experiments show that the C-SCI achieves higher accuracy than the original SCI for not only human-curated structural alignments but also low quality alignments produced by CLUSTAL W. Furthermore, the accuracy of the C-SCI on CLUSTAL W alignments is comparable with that of the original SCI on structural alignments generated with RAF for which 4.7-fold expensive computational time is required on average. © 2010 World Scientific Publishing Co. Pte. Ltd.

Kawahara T.,Japan Biological Informatics Consortium JBIC | Izumikawa M.,Japan Biological Informatics Consortium JBIC | Takagi M.,Japan Biological Informatics Consortium JBIC | Shin-Ya K.,Japan National Institute of Advanced Industrial Science and Technology
Organic Letters | Year: 2012

JBIR-129 was isolated as the potent cytotoxic compound, which consists of the 34-membered polyol macrolide skeleton with five sugar moieties. The relative configuration of the aglycone moiety (C7-C27 and C33-C39) was established by the J-based configuration analysis using vicinal 1H-1H (from 1H NMR and PS-DQF-COSY spectra) and long-range 1H-13C coupling constants (from sge-HETLOC and several J-resolved HMBC spectra) with steric information obtained from ROESY. © 2012 American Chemical Society.

Kawahara T.,Japan Biological Informatics Consortium JBIC | Hwang J.-H.,Japan Biological Informatics Consortium JBIC | Izumikawa M.,Japan Biological Informatics Consortium JBIC | Hashimoto J.,Japan Biological Informatics Consortium JBIC | And 2 more authors.
Journal of Natural Products | Year: 2012

New 34-membered polyol macrolides JBIR-129 (1) and JBIR-139 (2) were isolated from the culture of the terrestrial Streptomyces RK74. The planar structures of 1 and 2 were established on the basis of 1D and 2D NMR, ESI-TOF-MS, IR, and UV spectra. The relative configurations of the sugar units were determined by analyzing vicinal 1H-1H coupling constants and steric information. Both 1 and 2 showed cytotoxic activity against human ovarian adenocarcinoma SKOV-3 cells with IC50 values of 0.3 and 0.4 μM, respectively. © 2012 The American Chemical Society and American Society of Pharmacognosy.

Yamaguchi K.,Japan Biological Informatics Consortium JBiC | Inoue M.,Japan Biological Informatics Consortium JBiC | Goshima N.,Japan National Institute of Advanced Industrial Science and Technology
Journal of Biomedicine and Biotechnology | Year: 2011

Cationic peptides termed protein transduction domains (PTDs) have been shown to cross biological membranes efficiently. However, proteins transduced by PTDs become entrapped within the endosomal vesicles and are not delivered into organelles. We have developed a novel protein delivery system to enhance the proton sponge effect, which results in rupture of the endosomes, by using a mixture of Wr-T transporter peptide and a commercially available cationic lipid reagent. This peptide and cationic lipid reagent mixture efficiently delivers a variety of cargo proteins into living cells by releasing them from the endosomes. Copyright © 2011 Kei Yamaguchi et al.

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