Antimicrobial Peptide Mimetics Based on a Diphenylacetylene Scaffold: Synthesis, Conformational Analysis, and Activity
| العنوان: | Antimicrobial Peptide Mimetics Based on a Diphenylacetylene Scaffold: Synthesis, Conformational Analysis, and Activity |
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| المؤلفون: | Jinghui Luo, James Luccarelli, Alysha G. Elliott, Andrew D. Hamilton, Masanobu Nagano, Hayden Peacock, Sónia Troeira Henriques, David J. Craik, Aurélie H. Benfield |
| المصدر: | ChemMedChem. 15:1932-1939 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Erythrocytes, Peptidomimetic, Lipid Bilayers, Antimicrobial peptides, Molecular Conformation, Peptide, Microbial Sensitivity Tests, Hemolysis, 01 natural sciences, Biochemistry, chemistry.chemical_compound, Drug Discovery, Amphiphile, Animals, General Pharmacology, Toxicology and Pharmaceutics, Diphenylacetylene, Pharmacology, chemistry.chemical_classification, Bacteria, 010405 organic chemistry, Organic Chemistry, Antimicrobial, Combinatorial chemistry, Anti-Bacterial Agents, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Membrane, chemistry, Alkynes, Liposomes, Molecular Medicine, Peptidomimetics, Rabbits, Antibacterial activity |
| الوصف: | Mimics of natural antimicrobial peptides are promising compounds to fight the rising threat of multi-drug resistant bacteria. Here we report the design, synthesis and conformational analysis of a new class of antimicrobial peptide mimetics incorporating a diphenylacetylene scaffold. Within a small set of compounds, we observe a correlation between amphiphilicity, the efficiency of partitioning into negatively charged membranes and antibacterial activity. The most amphiphilic compound, which contains four isoleucine residues and four lysine residues, displays species-selective antibacterial activity (most active against Bacillus subtills) and low haemolytic activity. Solution-phase conformational analysis of this compound indicates that a defined structure is adopted in the presence of negatively charged phospholipid membranes and aqueous 2,2,2-trifluoroethanol but not in water. A conformation model indicates that the cationic and hydrophobic functional groups are segregated. These results may inform the development of highly selective antimicrobial peptide mimetics for therapeutic applications. |
| تدمد: | 1860-7187 1860-7179 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d0a62c00a8c207939f898edee5bf2865 https://doi.org/10.1002/cmdc.202000474 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....d0a62c00a8c207939f898edee5bf2865 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18607187 18607179 |
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