Truncation and non-natural amino acid substitution studies on HTLV-I protease hexapeptidic inhibitors

Jeffrey-Tri Nguyen; Meihui Zhang; Henri-Obadja Kumada; Ayako Itami; Keiji Nishiyama; Tooru Kimura; Maosheng Cheng; Yoshio Hayashi; Yoshiaki Kiso

doi:10.1016/j.bmcl.2007.10.066

Truncation and non-natural amino acid substitution studies on HTLV-I protease hexapeptidic inhibitors

Bioorg Med Chem Lett. 2008 Jan 1;18(1):366-70. doi: 10.1016/j.bmcl.2007.10.066. Epub 2007 Oct 24.

Authors

Jeffrey-Tri Nguyen¹, Meihui Zhang, Henri-Obadja Kumada, Ayako Itami, Keiji Nishiyama, Tooru Kimura, Maosheng Cheng, Yoshio Hayashi, Yoshiaki Kiso

Affiliation

¹ Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science and 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.

PMID: 18006315
DOI: 10.1016/j.bmcl.2007.10.066

Abstract

The culprit behind adult T-cell leukemia, myelopathy/tropical paraparesis, and a plethora of inflammatory diseases is the human T-cell leukemia virus type 1 (HTLV-I). We recently unveiled a potent hexapeptidic HTLV-I protease inhibitor, KNI-10166, composed mostly of natural amino acid residues. Herein, we report the derivation of potent tetrapeptidic inhibitor KNI-10516, possessing only non-natural amino acid residues.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Substitution
Amino Acids / chemistry*
Amino Acids / pharmacology*
Human T-lymphotropic virus 1 / enzymology*
Oligopeptides / chemistry*
Oligopeptides / pharmacology*
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacology*
Structure-Activity Relationship
Substrate Specificity

Substances

Amino Acids
Oligopeptides
Protease Inhibitors