Maintaining potent HTLV-I protease inhibition without the P3-cap moiety in small tetrapeptidic inhibitors

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1832-7. doi: 10.1016/j.bmcl.2011.01.048. Epub 2011 Jan 15.


The human T cell lymphotropic/leukemia virus type 1 (HTLV-I) causes adult T cell lymphoma/leukemia. The virus is also responsible for chronic progressive myelopathy and several inflammatory diseases. To stop the manufacturing of new viral components, in our previous reports, we derived small tetrapeptidic HTLV-I protease inhibitors with an important amide-capping moiety at the P(3) residue. In the current study, we removed the P(3)-cap moiety and, with great difficulty, optimized the P(3) residue for HTLV-I protease inhibition potency. We discovered a very potent and small tetrapeptidic HTLV-I protease inhibitor (KNI-10774a, IC(50)=13 nM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Human T-lymphotropic virus 1 / enzymology*
  • Models, Molecular
  • Oligopeptides / pharmacology*
  • Protease Inhibitors / pharmacology*


  • Oligopeptides
  • Protease Inhibitors