Synthesis and activity of tetrapeptidic HTLV-I protease inhibitors possessing different P3-cap moieties

Bioorg Med Chem. 2008 May 15;16(10):5795-802. doi: 10.1016/j.bmc.2008.03.055. Epub 2008 Mar 27.

Abstract

The causative agent behind adult T-cell leukemia and tropical spastic paraparesis/HTLV-I-associated myelopathy is the human T-cell leukemia virus type 1 (HTLV-I). Tetrapeptidic HTLV-I protease inhibitors were designed on a previously reported potent inhibitor KNI-10516, with modifications at the P(3)-cap moieties. All the inhibitors showed high HIV-1 protease inhibitory activity (over 98% inhibition at 50nM) and most exhibited highly potent inhibition against HTLV-I protease (IC(50) values were less than 100nM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Binding Sites
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • HIV Protease / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Conformation
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Oligopeptides
  • Protease Inhibitors
  • Aspartic Acid Endopeptidases
  • HIV Protease
  • HTLV-1 protease
  • p16 protease, Human immunodeficiency virus 1