Crystal structures of HIV-1 reverse transcriptase with picomolar inhibitors reveal key interactions for drug design

J Am Chem Soc. 2012 Dec 5;134(48):19501-3. doi: 10.1021/ja3092642. Epub 2012 Nov 19.

Abstract

X-ray crystal structures at 2.9 Å resolution are reported for two complexes of catechol diethers with HIV-1 reverse transcriptase. The results help elucidate the structural origins of the extreme antiviral activity of the compounds. The possibility of halogen bonding between the inhibitors and Pro95 is addressed. Structural analysis reveals key interactions with conserved residues P95 and W229 of importance for design of inhibitors with high potency and favorable resistance profiles.

Publication types

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

MeSH terms

  • Antiviral Agents / chemistry*
  • Bromine / chemistry
  • Crystallography, X-Ray
  • Drug Design*
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / chemistry*
  • Halogens / chemistry*
  • Humans
  • Hydrogen Bonding
  • Inhibitory Concentration 50
  • Models, Molecular*
  • Reverse Transcriptase Inhibitors / chemistry*

Substances

  • Antiviral Agents
  • Halogens
  • Reverse Transcriptase Inhibitors
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • Bromine