title: Synthesis and evaluation of pseudopeptide analogues of a specific CXCR4 inhibitor, T140: the insertion of an (E)-alkene dipeptide isostere into the betaII'-turn moiety.
abstract: A 14-residue peptide, T140, strongly inhibits the T-cell line-tropic HIV-1 (X4-HIV-1) infection, since this peptide functions as a specific antagonist against a chemokine receptor, CXCR4. T140 takes an antiparallel beta-sheet structure with a type II' beta-turn. In the present paper, we have designed and synthesized several T140 analogues, in which an (E)-alkene dipeptide isostere was inserted into the type II' beta-turn moiety, as a bridging study to develop nonpeptidic CXCR4 inhibitors. It has been proven that the turn region of T140 can be replaced by the above surrogate with the maintenance of strong anti-HIV activity.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan. tamamura@pharm.kyoto-u.ac.jp
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tamamura
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hiramatsu
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Akane
authors.initials: A
authors.lastname: Omagari
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakashima
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Terumichi
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Akira
authors.initials: A
authors.lastname: Otaka
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004151:Dipeptides / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D017433:Protein Structure, Secondary; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
chemical_list: D019380:Anti-HIV Agents; D004151:Dipeptides; D009842:Oligopeptides; D019718:Receptors, CXCR4; C116977:T140 peptide