Synthesis and evaluation of pseudopeptide analogues of a specific CXCR4 inhibitor, T140: The insertion of an (E)-alkene dipeptide isostere into the βII′-turn moiety
| Autor: | Kenichi Hiramatsu, Terumichi Nakagawa, Akane Omagari, Hideki Nakashima, Nobutaka Fujii, Yoshihiro Kuroda, Kazuhide Miyamoto, Naoki Yamamoto, Hirokazu Tamamura, Akira Otaka, Shinya Oishi |
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| Rok vydání: | 2002 |
| Předmět: |
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Molecular Receptors CXCR4 CXCR4 Inhibitor Anti-HIV Agents Isostere Stereochemistry Clinical Biochemistry Pharmaceutical Science Peptide Microbial Sensitivity Tests Biochemistry Chemical synthesis Protein Structure Secondary Inhibitory Concentration 50 chemistry.chemical_compound Drug Discovery Tumor Cells Cultured Peptide synthesis Humans Moiety Calcium Signaling Molecular Biology chemistry.chemical_classification Dipeptide Organic Chemistry Dipeptides Cyclic peptide chemistry HIV-1 Molecular Medicine Oligopeptides Cell Division |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 12:923-928 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/s0960-894x(02)00041-0 |
| Popis: | 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 β-sheet structure with a type II′ β-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′ β-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. |
| Databáze: | OpenAIRE |
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