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

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

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 languageEnglish
Pages (from-to)616-621
Number of pages6
JournalOrganic and Biomolecular Chemistry
Volume8
Issue number3
DOIs
Publication statusPublished - 2010 Feb 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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