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ID: ALA1135248

Journal: Bioorg Med Chem Lett

Title: Synthesis and evaluation of pseudopeptide analogues of a specific CXCR4 inhibitor, T140: the insertion of an (E)-alkene dipeptide isostere into the betaII'-turn moiety.

Authors: Tamamura H, Hiramatsu K, Miyamoto K, Omagari A, Oishi S, Nakashima H, Yamamoto N, Kuroda Y, Nakagawa T, Otaka A, Fujii N.

Abstract: A 14-residue peptide, T140, strongly inhibits the T-cell line-tropic HIV-1 (X4-HIV-1) infection, since this peptide functions as a specific antagonist against a chemokine receptor, CXCR4. T140 takes an antiparallel beta-sheet structure with a type II' beta-turn. In the present paper, we have designed and synthesized several T140 analogues, in which an (E)-alkene dipeptide isostere was inserted into the type II' beta-turn moiety, as a bridging study to develop nonpeptidic CXCR4 inhibitors. It has been proven that the turn region of T140 can be replaced by the above surrogate with the maintenance of strong anti-HIV activity.

CiteXplore: 11958995

DOI: 10.1016/s0960-894x(02)00041-0