Chipping at large, potent human T-cell leukemia virus type 1 protease inhibitors to uncover smaller, equipotent inhibitors.
The human T-cell leukemia virus type 1 (HTLV-I) causes adult T-cell leukemia and several severe chronic diseases. HTLV-I protease (PR) inhibition stops the propagation of the virus. Herein, truncation studies were performed on potent octapeptidic HTLV-I PR inhibitor KNI-10161 to derive small hexapeptide KNI-10127 with some loss in activity. After performing residue-substitution studies on compound KNI-10127, HTLV-I PR inhibitory activity was recovered in inhibitor KNI-10166.
Kimura
Tooru
T
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science and 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan.
Nguyen
Jeffrey-Tri
JT
Maegawa
Hikoichiro
H
Nishiyama
Keiji
K
Arii
Yasuhiro
Y
Matsui
Yasuko
Y
Hayashi
Yoshio
Y
Kiso
Yoshiaki
Y
D000328:Adult; D002908:Chronic Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D008958:Models, Molecular; D008970:Molecular Weight; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*
D017320:HIV Protease Inhibitors; D009842:Oligopeptides