Discovery of HIV fusion inhibitors targeting gp41 using a comprehensive α-helix mimetic library

Bioorg Med Chem Lett. 2012 Apr 15;22(8):2861-5. doi: 10.1016/j.bmcl.2012.02.062. Epub 2012 Mar 3.


The evaluation of a comprehensive α-helix mimetic library for binding the gp41 NHR hydrophobic pocket recognizing an intramolecular CHR α-helix provided a detailed depiction of structural features required for binding and led to the discovery of small molecule inhibitors (K(i) 0.6-1.3 μM) that not only match or exceed the potency of those disclosed over the past decade, but that also exhibit effective activity in a cell-cell fusion assay (IC(50) 5-8 μM).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-HIV Agents / chemistry*
  • Drug Discovery*
  • HIV Envelope Protein gp41 / metabolism*
  • HIV Fusion Inhibitors / chemistry*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Mimicry*
  • Molecular Structure
  • Protein Structure, Secondary
  • Small Molecule Libraries / chemistry*


  • Anti-HIV Agents
  • HIV Envelope Protein gp41
  • HIV Fusion Inhibitors
  • Small Molecule Libraries