2. Academic Validation
  3. 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

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

  • Bioorg Med Chem Lett. 2002 Mar 25;12(6):923-8. doi: 10.1016/s0960-894x(02)00041-0.
Hirokazu Tamamura 1,  Kenichi Hiramatsu,  Kazuhide Miyamoto,  Akane Omagari,  Shinya Oishi,  Hideki Nakashima,  Naoki Yamamoto,  Yoshihiro Kuroda,  Terumichi Nakagawa,  Akira Otaka,  Nobutaka Fujii
Affiliations

Affiliation

  • 1 Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan. tamamura@pharm.kyoto-u.ac.jp
PMID: 11958995 DOI: 10.1016/s0960-894x(02)00041-0
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.

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