Bridged α-helix mimetic small molecules

Chem Commun (Camb). 2019 Oct 31;55(88):13311-13314. doi: 10.1039/c9cc03627j.

Abstract

Herein, we report a strategy for generating conformationally restricted α-helix mimetic small molecules by introducing covalent bridges that limit rotation about the central axis of α-helix mimetics. We demonstrate that the bridged α-helix mimetics have enhanced binding affinity and specificity to the target protein due to the restricted conformation as well as extra interaction of the bridge with the protein surface.

MeSH terms

  • Heterocyclic Compounds, Bridged-Ring / chemistry*
  • Heterocyclic Compounds, Bridged-Ring / pharmacology
  • Humans
  • Jurkat Cells
  • Models, Molecular
  • Molecular Conformation
  • Myeloid Cell Leukemia Sequence 1 Protein / antagonists & inhibitors
  • Myeloid Cell Leukemia Sequence 1 Protein / chemistry*
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology

Substances

  • Heterocyclic Compounds, Bridged-Ring
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Small Molecule Libraries