Discovery of indolyl-containing peptides as novel antibacterial agents targeting tryptophanyl-tRNA synthetase
| Autor: | Zhiling Zhu, Xiaodan Qiu, Lianqi Sun, Shuo Zhang, Ran Wang, Guangzhi Shan, Zhuorong Li |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Staphylococcus aureus
Indoles medicine.drug_class Antibiotics Tryptophan-tRNA Ligase Tripeptide Tryptophanyl-tRNA synthetase Microbial Sensitivity Tests 01 natural sciences 03 medical and health sciences Antibiotic resistance Drug Discovery medicine Staphylococcus epidermidis Enzyme Inhibitors 030304 developmental biology Antibacterial agent Pharmacology 0303 health sciences biology Molecular Structure 010405 organic chemistry Chemistry 0104 chemical sciences Anti-Bacterial Agents Biochemistry Enzyme inhibitor biology.protein Molecular Medicine Peptides |
| Zdroj: | Future medicinal chemistry. 12(10) |
| ISSN: | 1756-8927 |
| Popis: | Background: There is an urgent need for antibiotics with novel structures and unexploited targets to counteract bacterial resistance. Methodology & results: Novel tryptophanyl-tRNA synthetase inhibitors were discovered based on virtual screening, surface plasmon resonance binding, enzymatic activity assay and antibacterial activity evaluation. Of the 29 peptide derivatives tested for antibacterial activity, some inhibited the growth of both Staphylococcus aureus and Staphylococcus epidermidis. A13 and A15 exhibited antibacterial activity against methicillin-resistant S. aureus NRS384 at an 8 μg/ml minimum inhibitory concentration. A13 snugly docked into the active site, explaining its improved inhibitory activity. Conclusion: Our results provide us with new structural clues to develop more potent tryptophanyl-tRNA synthetase inhibitors and lay a solid foundation for future drug design efforts. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|