title: Effect of prime-site sequence of retro-inverso-modified HTLV-1 protease inhibitor.
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.
authors.affiliation: Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kita-ku, Kyoto 603-8334, Japan.
authors.forename: Chiyuki
authors.initials: C
authors.lastname: Awahara
authors.affiliation: Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kita-ku, Kyoto 603-8334, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Tatsumi
authors.affiliation: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Furuta
authors.affiliation: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Shinjoh
authors.affiliation: Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konno
authors.affiliation: Department of Chemistry, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nosaka
authors.affiliation: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Yasunao
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan. Electronic address: akaji@mb.kyoto-phu.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Akaji
mesh_terms: D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D005021:Ethylamines / Q000737:chemistry; D015368:Human T-lymphotropic virus 1 / Q000201:enzymology*; D006801:Humans; D011480:Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D005021:Ethylamines; D011480:Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; C079711:HTLV-1 protease; C041564:ethylamine
keywords: HTLV-1 protease; Hydroxyethylamine isoster; Inhibitor; Retro-inverso