title: Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres.
abstract: A set of cyclic peptide analogues of a selective CXCR4 antagonist FC131 [cyclo(-d-Tyr-Arg-Arg-Nal-Gly-)] were synthesized and bioevaluated. Using (E)-alkene and (Z)-fluoroalkene dipeptide isosteres for Arg-Arg and Arg-Nal substructures, indispensable or the partial contribution of the two peptide bonds to the CXCR4 antagonism and anti-HIV activity was demonstrated. FC131 and the analogues were shown to selectively inhibit SDF-1 binding to CXCR4, whereas no inhibition of binding of SDF-1 to CXCR7 was observed.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Narumi
authors.forename: Ryoko
authors.initials: R
authors.lastname: Hayashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Tomita
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Noriko
authors.initials: N
authors.lastname: Tanahara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohno
authors.forename: Takeshi
authors.initials: T
authors.lastname: Naito
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kodama
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000595:Amino Acid Sequence; D002460:Cell Line; D004151:Dipeptides / Q000737:chemistry*; D006678:HIV / Q000187:drug effects; D054879:Halogenation; D006801:Humans; D020128:Inhibitory Concentration 50; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D055672:Static Electricity; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D004151:Dipeptides; D010456:Peptides, Cyclic; D019718:Receptors, CXCR4