Inhibitor profiling of the Pseudomonas aeruginosa virulence factor LasB using N-alpha mercaptoamide template-based inhibitors
| العنوان: | Inhibitor profiling of the Pseudomonas aeruginosa virulence factor LasB using N-alpha mercaptoamide template-based inhibitors |
|---|---|
| المؤلفون: | Pat Harriott, Brett Greer, George Cathcart, Brian Walker, Brendan Gilmore |
| المصدر: | Bioorganicmedicinal chemistry letters. 19(21) |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, Peptide, Biochemistry, chemistry.chemical_compound, Bacterial Proteins, Catalytic Domain, Drug Discovery, Peptide synthesis, Protease Inhibitors, Sulfhydryl Compounds, Binding site, Peptide library, Molecular Biology, Antibacterial agent, chemistry.chemical_classification, Dipeptide, Binding Sites, biology, Chemistry, Organic Chemistry, Metalloendopeptidases, Dipeptides, Amides, Amino acid, Enzyme inhibitor, Pseudomonas aeruginosa, biology.protein, Molecular Medicine |
| الوصف: | We report on the synthesis and biological evaluation of a focussed library of N-alpha mercaptoamide containing dipeptides as inhibitors of the zinc metallopeptidase Pseudomonas aeruginosa elastase (LasB, EC 3.4.24.26). The aim of the study was to derive an inhibitor profile for LasB with regard to mapping the S'1 binding site of the enzyme. Consequently, a focussed library of 160 members has been synthesised, using standard Fmoc-solid phase methods (on a Rink-amide resin), in which a subset of amino acids including examples of those with basic (Lys, Arg), aromatic (Phe, Trp), large aliphatic (Val, Leu) and acidic (Asp, Glu) side-chains populated the P'2 position of the inhibitor sequence and all 20 natural amino acids were incorporated, in turn, at the P'1 position. The study has revealed a preference for aromatic and/or large aliphatic amino acids at P'1 and a distinct bias against acidic residues at P'2. Ten inhibitor sequences were discovered that exhibited sub to low micromolar Ki values. |
| تدمد: | 1464-3405 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::80821456ae9ab2a71d9e250e505e61e0Test https://pubmed.ncbi.nlm.nih.gov/19773163Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....80821456ae9ab2a71d9e250e505e61e0 |
| قاعدة البيانات: | OpenAIRE |
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