Certification of the Critical Importance of l-3-(2-Naphthyl)alanine at Position 3 of a Specific CXCR4 Inhibitor, T140, Leads to an Exploratory Performance of Its Downsizing Study
| Autor: | Akane Omagari, Shinya Oishi, Hirokazu Tamamura, Kenichi Hiramatsu, Hiromu Habashita, Nobutaka Fujii, Hideki Nakashima, Akira Otaka, Kazuyo Gotoh, Naoki Yamamoto, Taisei Kanamoto |
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| Rok vydání: | 2002 |
| Předmět: |
Receptors
CXCR4 CXCR4 Inhibitor Anti-HIV Agents Cell Survival medicine.drug_class Stereochemistry Clinical Biochemistry Pharmaceutical Science Carboxamide Naphthalenes Biochemistry Structure-Activity Relationship chemistry.chemical_compound Chemokine receptor Drug Discovery Tumor Cells Cultured Peptide synthesis medicine Aromatic amino acids Humans Structure–activity relationship Amino Acid Sequence Calcium Signaling Molecular Biology Peptide sequence Alanine Organic Chemistry chemistry HIV-1 Molecular Medicine Oligopeptides |
| Zdroj: | Bioorganic & Medicinal Chemistry. 10:1417-1426 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/s0968-0896(01)00419-9 |
| Popis: | We have previously found that a 14-amino acid residue-peptide, T140, inhibits infection of target cells by T cell line-tropic HIV-1 (X4-HIV-1) through its specific binding to a chemokine receptor, CXCR4. Here, the importance of an L-3-(2-naphthyl)alanine (Nal) residue at position 3 in T140 for high anti-HIV activity and inhibitory activity against Ca(2+) mobilization induced by stromal cell-derived factor (SDF)-1alpha-stimulation through CXCR4 has initially been shown by the synthesis and biological evaluation of several analogues, where Nal(3) is substituted by diverse aromatic amino acids. Next, the order of the N-terminal 3 residues (Arg(1)-Arg(2)-Nal(3)) has been proved to be important from the structure--activity relationship (SAR) study shuffling these residues. Based on these results, we have found 10-residue peptides possessing modest anti-HIV activity by systematic antiviral evaluation of a series of synthetic, shortened analogues of T140. |
| Databáze: | OpenAIRE |
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