James WellsSummaryAffiliation: University of California Country: USA Publications
Research Grants
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Detail Information
Publications
Disulfide trapping to localize small-molecule agonists and antagonists for a G protein-coupled receptorElizabeth Buck
Sunesis Pharmaceuticals, 341 Oyster Point Boulevard, South San Francisco, CA 94080, USA
Proc Natl Acad Sci U S A 102:2719-24. 2005..Selective ligand trapping by reversible disulfide formation may serve to nucleate the development of small-molecule mimics...- A common allosteric site and mechanism in caspasesJustin M Scheer
Department of Pharmaceutical Chemistry, University of California, 1700 4th Street, San Francisco, CA 94143, USA
Proc Natl Acad Sci U S A 103:7595-600. 2006..Together, these studies show a general small-molecule-binding site for functionally reversing the zymogen activation of caspases and suggest a common regulatory site for the allosteric control of inflammation and apoptosis... 
Reaching for high-hanging fruit in drug discovery at protein-protein interfacesJames A Wells
Department of Pharmaceutical Chemistry, University of California at San Francisco, 1700 4th Street 503A, San Francisco, California 94156, USA
Nature 450:1001-9. 2007..Some of these small molecules are now making their way through clinical trials, so this high-hanging fruit might not be far out of reach...- Global sequencing of proteolytic cleavage sites in apoptosis by specific labeling of protein N terminiSami Mahrus
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA
Cell 134:866-76. 2008..Strikingly, we also find that a disproportionate number of caspase substrates physically interact, suggesting that these dimeric proteases target protein complexes and networks to elicit apoptosis... - Two-state selection of conformation-specific antibodiesJunjun Gao
Department of Pharmaceutical Chemistry, University of California, 1700 4th Street, San Francisco, CA 94143, USA
Proc Natl Acad Sci U S A 106:3071-6. 2009..These studies demonstrate a general strategy for producing conformation-selective antibodies and show their utility for probing the distribution of caspase-1 conformational states in vitro and in cells... - Tags for labeling protein N-termini with subtiligase for proteomicsHikari A I Yoshihara
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158 2330, USA
Bioorg Med Chem Lett 18:6000-3. 2008..These new tags should expand the utility of subtiligase for the proteomic study of N-termini... - Small-molecule inhibitors of protein-protein interactions: progressing towards the dreamMichelle R Arkin
Sunesis Pharmaceuticals, 341 Oyster Point Boulevard, South San Francisco, California 94080, USA
Nat Rev Drug Discov 3:301-17. 2004 - Tethering: fragment-based drug discoveryDaniel A Erlanson
Sunesis Pharmaceuticals, Inc, 341 Oyster Point Boulevard, South San Francisco, California 94080, USA
Annu Rev Biophys Biomol Struct 33:199-223. 2004.... - Computational approach to site-directed ligand discoveryGergely Toth
Locus Pharmaceuticals, Blue Bell, Pennsylvania 19422, USA
Proteins 68:551-60. 2007..The SCI&FI method provides a complementary approach to experimental tethering. Initial validation of the SCI&FI method is reported by predicting the 3D structure of two Interleukin-2 and an Interleukin-4 tethered-protein systems... - Searching for new allosteric sites in enzymesJeanne A Hardy
Sunesis Pharmaceuticals Inc, 341 Oyster Point Boulevard, South San Francisco, California 94080, USA
Curr Opin Struct Biol 14:706-15. 2004..By exploring recent structurally well-characterized examples, trends begin to emerge for both the modes of binding and mechanisms of inhibition... - Site-specific disulfide capture of agonist and antagonist peptides on the C5a receptorElizabeth Buck
Sunesis Pharmaceuticals Inc, South San Francisco, California 94080, USA
J Biol Chem 280:4009-12. 2005..These data help to further refine the binding mode for C5a to the C5aR and suggest an approach and a binding site that may be applicable to studying other peptide binding receptors... - Discovery of an allosteric site in the caspasesJeanne A Hardy
Sunesis Pharmaceuticals, Inc, 341 Oyster Point Boulevard, South San Francisco, CA 94080, USA
Proc Natl Acad Sci U S A 101:12461-6. 2004..This approach may be useful to identify new allosteric sites from natural or engineered cysteines, to study allosteric transitions in proteins, and to nucleate drug discovery efforts... - Apo cytochrome c inhibits caspases by preventing apoptosome formationAngel G Martin
Apoptosis Section, Laboratory of Protein Dynamics and Signaling, NCI-Frederick, Frederick, MD 21702, USA
Biochem Biophys Res Commun 319:944-50. 2004..Furthermore, using purified proteins and size exclusion chromatography we show that apo cytochrome c prevents holo cytochrome c-dependent apoptosome formation... - Potent small-molecule binding to a dynamic hot spot on IL-2Christopher D Thanos
Sunesis Pharmaceuticals, Inc, 341 Oyster Point Boulevard, South San Francisco, CA 94080, USA
J Am Chem Soc 125:15280-1. 2003..Therefore, fragment assembly methods offer the stochastic advantage of finding fragments in flexible protein regions where structural changes are unpredictable... - Direct activation of the apoptosis machinery as a mechanism to target cancer cellsJack T Nguyen
Sunesis Pharmaceuticals, 341 Oyster Point Boulevard, South San Francisco, CA 94080, USA
Proc Natl Acad Sci U S A 100:7533-8. 2003..These findings suggest that direct activation of the basic apoptosis machinery may be a viable mechanism to selectively target cancer... - Binding of small molecules to an adaptive protein-protein interfaceMichelle R Arkin
Department of Biology, Sunesis Pharmaceuticals, South San Francisco, CA 94080 1913, USA
Proc Natl Acad Sci U S A 100:1603-8. 2003..Thus, the adaptive nature of a protein-protein interface provides sites for small molecules to bind and underscores the challenge of applying structure-based design strategies that cannot accurately predict a dynamic protein surface...
Research Grants
- Direct Chemical Activators of CaspasesJames A Wells; Fiscal Year: 2010..Moreover, we will define the therapeutic window for these compounds in cells and potential pharmacodynamic and biomarkers for transitioning these to animal studies and ultimately humans. ..
- Direct Chemical Activators of CaspasesJames A Wells; Fiscal Year: 2011..Moreover, we will define the therapeutic window for these compounds in cells and potential pharmacodynamic and biomarkers for transitioning these to animal studies and ultimately humans. ..
- HIV Integrase Drug Discovery Using Tethering TechnologyJames Wells; Fiscal Year: 2003..abstract_text> ..
- Global Analysis of Proteolysis in ApoptosisJames A Wells; Fiscal Year: 2010..Thus, in addition to mapping the process of apoptosis and demonstrating a general degradomics method, the proposed work may identify new drug targets for the development of cancer therapies. ..
- Site-specific Allosteric Inhibitors for Inflammatory CaspasesJames A Wells; Fiscal Year: 2010..These drugs would be anticipated to have more selectivity and less side effects than existing drugs. ..
- Site-specific Allosteric Inhibitors for Inflammatory CaspasesJames Wells; Fiscal Year: 2007..These drugs would be anticipated to have more selectivity and less side effects than existing drugs. ..
- Activators of Procaspase-7James Wells; Fiscal Year: 2006..The identification of lead compounds with drug-like properties that allosterically induce procaspase-7 activation would be a significant and novel advancement in cancer therapeutics. ..
- Global Analysis of Proteolysis in ApoptosisJames A Wells; Fiscal Year: 2010..Thus, in addition to mapping the process of apoptosis and demonstrating a general degradomics method, the proposed work may identify new drug targets for the development of cancer therapies. ..