Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Org Biomol Chem. 2010 Feb 7;8(3):616-21. doi: 10.1039/b917236j. Epub 2009 Dec 4.
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.
一组 CXCR4 选择性拮抗剂 FC131 [cyclo(-d-Tyr-Arg-Arg-Nal-Gly-)]的环肽类似物被合成并进行了生物评价。使用 (E)-烯烃和 (Z)-氟烯烃二肽等价物替代 Arg-Arg 和 Arg-Nal 亚结构，证明了两个肽键对 CXCR4 拮抗作用和抗 HIV 活性的不可或缺或部分贡献。结果表明，FC131 及其类似物选择性抑制 SDF-1 与 CXCR4 的结合，而对 SDF-1 与 CXCR7 的结合没有抑制作用。
