Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres

Tetsuo Narumi; Ryoko Hayashi; Kenji Tomita; Kazuya Kobayashi; Noriko Tanahara; Hiroaki Ohno; Takeshi Naito; Eiichi Kodama; Masao Matsuoka; Shinya Oishi; Nobutaka Fujii

doi:10.1039/b917236j

Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres

Tetsuo Narumi, Ryoko Hayashi, Kenji Tomita, Kazuya Kobayashi, Noriko Tanahara, Hiroaki Ohno, Takeshi Naito, Eiichi Kodama, Masao Matsuoka, Shinya Oishi, Nobutaka Fujii

IRIDeS - Disaster Medical Science Division

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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.

Original language	English
Pages (from-to)	616-621
Number of pages	6
Journal	Organic and Biomolecular Chemistry
Volume	8
Issue number	3
DOIs	https://doi.org/10.1039/b917236j
Publication status	Published - 2010

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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.",

author = "Tetsuo Narumi and Ryoko Hayashi and Kenji Tomita and Kazuya Kobayashi and Noriko Tanahara and Hiroaki Ohno and Takeshi Naito and Eiichi Kodama and Masao Matsuoka and Shinya Oishi and Nobutaka Fujii",

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TY - JOUR

T1 - Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres

AU - Narumi, Tetsuo

AU - Hayashi, Ryoko

AU - Tomita, Kenji

AU - Kobayashi, Kazuya

AU - Tanahara, Noriko

AU - Ohno, Hiroaki

AU - Naito, Takeshi

AU - Kodama, Eiichi

AU - Matsuoka, Masao

AU - Oishi, Shinya

AU - Fujii, Nobutaka

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

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JO - Organic and Biomolecular Chemistry

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Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres

Abstract

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