title: Maintaining potent HTLV-I protease inhibition without the P3-cap moiety in small tetrapeptidic inhibitors.
abstract: 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).
authors.affiliation: Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan.
authors.forename: Jeffrey-Tri
authors.initials: JT
authors.lastname: Nguyen
authors.forename: Keiko
authors.initials: K
authors.lastname: Kato
authors.forename: Henri-Obadja
authors.initials: HO
authors.lastname: Kumada
authors.forename: Koushi
authors.initials: K
authors.lastname: Hidaka
authors.forename: Tooru
authors.initials: T
authors.lastname: Kimura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
mesh_terms: D018360:Crystallography, X-Ray; D015368:Human T-lymphotropic virus 1 / Q000201:enzymology*; D008958:Models, Molecular; D009842:Oligopeptides / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*
chemical_list: D009842:Oligopeptides; D011480:Protease Inhibitors