James Wells

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc Disulfide trapping to localize small-molecule agonists and antagonists for a G protein-coupled receptor
    Elizabeth Buck
    Sunesis Pharmaceuticals, 341 Oyster Point Boulevard, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 102:2719-24. 2005
  2. pmc A common allosteric site and mechanism in caspases
    Justin 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
  3. ncbi request reprint Reaching for high-hanging fruit in drug discovery at protein-protein interfaces
    James 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
  4. pmc Global sequencing of proteolytic cleavage sites in apoptosis by specific labeling of protein N termini
    Sami Mahrus
    Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA
    Cell 134:866-76. 2008
  5. pmc Two-state selection of conformation-specific antibodies
    Junjun 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
  6. pmc Tags for labeling protein N-termini with subtiligase for proteomics
    Hikari A I Yoshihara
    Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158 2330, USA
    Bioorg Med Chem Lett 18:6000-3. 2008
  7. ncbi request reprint Small-molecule inhibitors of protein-protein interactions: progressing towards the dream
    Michelle R Arkin
    Sunesis Pharmaceuticals, 341 Oyster Point Boulevard, South San Francisco, California 94080, USA
    Nat Rev Drug Discov 3:301-17. 2004
  8. ncbi request reprint Tethering: fragment-based drug discovery
    Daniel A Erlanson
    Sunesis Pharmaceuticals, Inc, 341 Oyster Point Boulevard, South San Francisco, California 94080, USA
    Annu Rev Biophys Biomol Struct 33:199-223. 2004
  9. ncbi request reprint Computational approach to site-directed ligand discovery
    Gergely Toth
    Locus Pharmaceuticals, Blue Bell, Pennsylvania 19422, USA
    Proteins 68:551-60. 2007
  10. ncbi request reprint Searching for new allosteric sites in enzymes
    Jeanne A Hardy
    Sunesis Pharmaceuticals Inc, 341 Oyster Point Boulevard, South San Francisco, California 94080, USA
    Curr Opin Struct Biol 14:706-15. 2004

Research Grants

  1. Direct Chemical Activators of Caspases
    James A Wells; Fiscal Year: 2010
  2. Direct Chemical Activators of Caspases
    James A Wells; Fiscal Year: 2011
  3. HIV Integrase Drug Discovery Using Tethering Technology
    James Wells; Fiscal Year: 2003
  4. Global Analysis of Proteolysis in Apoptosis
    James A Wells; Fiscal Year: 2010
  5. Site-specific Allosteric Inhibitors for Inflammatory Caspases
    James A Wells; Fiscal Year: 2010
  6. Site-specific Allosteric Inhibitors for Inflammatory Caspases
    James Wells; Fiscal Year: 2007
  7. Activators of Procaspase-7
    James Wells; Fiscal Year: 2006
  8. Global Analysis of Proteolysis in Apoptosis
    James A Wells; Fiscal Year: 2010

Collaborators

Detail Information

Publications16

  1. pmc Disulfide trapping to localize small-molecule agonists and antagonists for a G protein-coupled receptor
    Elizabeth 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...
  2. pmc A common allosteric site and mechanism in caspases
    Justin 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...
  3. ncbi request reprint Reaching for high-hanging fruit in drug discovery at protein-protein interfaces
    James 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...
  4. pmc Global sequencing of proteolytic cleavage sites in apoptosis by specific labeling of protein N termini
    Sami 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...
  5. pmc Two-state selection of conformation-specific antibodies
    Junjun 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...
  6. pmc Tags for labeling protein N-termini with subtiligase for proteomics
    Hikari 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...
  7. ncbi request reprint Small-molecule inhibitors of protein-protein interactions: progressing towards the dream
    Michelle R Arkin
    Sunesis Pharmaceuticals, 341 Oyster Point Boulevard, South San Francisco, California 94080, USA
    Nat Rev Drug Discov 3:301-17. 2004
  8. ncbi request reprint Tethering: fragment-based drug discovery
    Daniel A Erlanson
    Sunesis Pharmaceuticals, Inc, 341 Oyster Point Boulevard, South San Francisco, California 94080, USA
    Annu Rev Biophys Biomol Struct 33:199-223. 2004
    ....
  9. ncbi request reprint Computational approach to site-directed ligand discovery
    Gergely 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...
  10. ncbi request reprint Searching for new allosteric sites in enzymes
    Jeanne 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...
  11. ncbi request reprint Site-specific disulfide capture of agonist and antagonist peptides on the C5a receptor
    Elizabeth 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...
  12. pmc Discovery of an allosteric site in the caspases
    Jeanne 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...
  13. ncbi request reprint Apo cytochrome c inhibits caspases by preventing apoptosome formation
    Angel 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...
  14. ncbi request reprint Potent small-molecule binding to a dynamic hot spot on IL-2
    Christopher 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...
  15. pmc Direct activation of the apoptosis machinery as a mechanism to target cancer cells
    Jack 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...
  16. pmc Binding of small molecules to an adaptive protein-protein interface
    Michelle 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 Grants14

  1. Direct Chemical Activators of Caspases
    James 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. ..
  2. Direct Chemical Activators of Caspases
    James 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. ..
  3. HIV Integrase Drug Discovery Using Tethering Technology
    James Wells; Fiscal Year: 2003
    ..abstract_text> ..
  4. Global Analysis of Proteolysis in Apoptosis
    James 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. ..
  5. Site-specific Allosteric Inhibitors for Inflammatory Caspases
    James A Wells; Fiscal Year: 2010
    ..These drugs would be anticipated to have more selectivity and less side effects than existing drugs. ..
  6. Site-specific Allosteric Inhibitors for Inflammatory Caspases
    James Wells; Fiscal Year: 2007
    ..These drugs would be anticipated to have more selectivity and less side effects than existing drugs. ..
  7. Activators of Procaspase-7
    James 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. ..
  8. Global Analysis of Proteolysis in Apoptosis
    James 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. ..