Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres
Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres
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DOI：
10.1039/b917236j
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发表时间：
2010-01-01
影响因子：
3.2
通讯作者：
Fujii, Nobutaka
中科院分区：
文献类型：
--
作者：
Narumi, Tetsuo;Hayashi, Ryoko;Fujii, Nobutaka
合成了一系列选择性CXCR4拮抗剂FC131的环肽类似物[cyo(-D-Tyr-Arg-Nal-Gly-)]，并对其进行了生物活性评价。用(E)-烯烃和(Z)-氟烯烃二肽同位异构体作为Arg-Arg和Arg-al的亚结构，证明了这两个肽键对CXCR4的拮抗作用和抗HIV活性是不可或缺的或部分贡献的。FC131及其类似物选择性地抑制SDF-1与CXCR4的结合，而不抑制SDF-1与CXCR7的结合。
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.