Rapid Elaboration of Fragments into Leads by X-ray Crystallographic Screening of Parallel Chemical Libraries (REFiLX) Academic Article uri icon

abstract

  • A bottleneck in fragment-based lead development is the lack of systematic approaches to elaborate the initial fragment hits, which usually bind with low affinity to their target. Herein, we describe an analysis using X-ray crystallography of a diverse library of compounds prepared using microscale parallel synthesis. This approach yielded an 8-fold increase in affinity and detailed structural information for the resulting complex, providing an efficient and broadly applicable approach to early fragment development.

authors

  • Bentley, MR
  • Ilyichova, OV
  • Wang, Geqing
  • Williams, ML
  • Sharma, G
  • Alwan, WS
  • Whitehouse, RL
  • Mohanty, B
  • Scammells, PJ
  • Heras, Begona
  • Martin, JL
  • Totsika, M
  • Capuano, B
  • Doak, BC
  • Scanlon, MJ

publication date

  • 2020