First experimental identification of Ras-inhibitor binding interface using a water-soluble Ras ligand

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4217-22. doi: 10.1016/j.bmcl.2009.05.107. Epub 2009 May 30.

Abstract

By combining in the same molecule Ras-interacting aromatic moieties and a sugar, we prepared a water-soluble Ras ligand that binds Ras and inhibits guanine nucleotide exchange. With this compound it was possible to determine experimentally by a (15)N-edited HSQC NMR experiment the ligand-Ras binding interface.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Glucosides / chemical synthesis*
  • Glucosides / pharmacology
  • Guanine / chemistry
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy / methods
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • NIH 3T3 Cells
  • Protein Binding
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / pharmacology
  • ras Proteins / antagonists & inhibitors*
  • ras Proteins / metabolism

Substances

  • Antineoplastic Agents
  • Glucosides
  • Ligands
  • SCH 54292
  • Sulfonamides
  • Guanine
  • ras Proteins