Unexpected binding mode of a cyclic sulfamide HIV-1 protease inhibitor

J Med Chem. 1997 Mar 14;40(6):898-902. doi: 10.1021/jm960588d.

Abstract

Two cyclic, C2-symmetric HIV-1 protease inhibitors, one sulfamide and one urea derivative, both comprising phenyl ether groups in the P1/P1' positions, were cocrystallized with HIV-1 protease, and the crystal structures were determined to 2.0 A resolution. The structure of the urea 2 showed a conformation similar to that reported for the related urea 3 by Lam et al., while the sulfamide 1 adopted an unanticipated conformation in which the P1' and P2' side chains were transposed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azepines / chemistry*
  • Azepines / metabolism
  • Azepines / pharmacology
  • Binding Sites
  • Crystallization
  • Crystallography, X-Ray
  • HIV Protease / chemistry*
  • HIV Protease / metabolism
  • HIV Protease Inhibitors / chemistry*
  • HIV Protease Inhibitors / metabolism
  • HIV Protease Inhibitors / pharmacology
  • HIV-1 / enzymology*
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Protein Binding
  • Sulfonamides / chemistry*
  • Sulfonamides / metabolism
  • Sulfonamides / pharmacology

Substances

  • 1,3-dibenzyl-5,6--dihydroxy-4,7-di-(phenoxymethyl)-1,3-azepin-2-one
  • 1,3-dibenzyl-5,6-dihydroxy-4,7-di-(phenoxymethyl)-2-thia-1,3-azepine S,S-dioxide
  • Azepines
  • HIV Protease Inhibitors
  • Sulfonamides
  • HIV Protease