Effect of prime-site sequence of retro-inverso-modified HTLV-1 protease inhibitor

Bioorg Med Chem. 2014 Apr 15;22(8):2482-8. doi: 10.1016/j.bmc.2014.02.050. Epub 2014 Mar 4.

Abstract

The effects of additional substituents covering the prime-site of retro-inverso (RI)-modified HTLV-1 protease inhibitors containing a hydroxyethylamine isoster were clarified. Stereo-selective construction of the most potent isoster backbone was achieved by the Evans-aldol reaction. Addition of N-acetylated d-amino acid corresponding to the P2' site gave an RI-modified inhibitor showing superior inhibitory activity to the previous inhibitor. Inhibitory activities of the newly synthesized inhibitors suggest that partially modified RI inhibitors would interact with HTLV-1 protease in the same manner as the parent hydroxyethylamine inhibitor.

Keywords: HTLV-1 protease; Hydroxyethylamine isoster; Inhibitor; Retro-inverso.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Aspartic Acid Endopeptidases / chemistry*
  • Aspartic Acid Endopeptidases / metabolism
  • Ethylamines / chemistry
  • Human T-lymphotropic virus 1 / enzymology*
  • Humans
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / metabolism
  • Protein Binding

Substances

  • Ethylamines
  • Protease Inhibitors
  • Aspartic Acid Endopeptidases
  • HTLV-1 protease
  • ethylamine