Novel cyclic heptapeptides as potential therapeutics against methicillin-resistant Staphylococcus aureus infections
Abstract
Novel therapeutic agents for methicillin-resistant Staphylococcus aureus (MRSA) need to be developed because of the growing antibacterial resistance against MRSA. This study aimed to design and develop novel cyclic heptapeptides as potential antibacterial agents with improved efficacy and safety profiles against MRSA. Here, we designed 100 novel cyclic heptapeptides, and it was examined computationally and validated through experimental methods. The best three cyclic heptapeptides, such as Tyr6, Gly6, and Ala6, showed the binding energy between - 10.9 and - 11.23 kcal/mol. These three cyclic heptapeptides were synthesised with 94% purity using the solid-phase peptide synthesis (SPPS) strategy, showing the 18-mm zone of inhibition against MRSA in the study of biological activities. Antibacterial evaluation against MRSA, methicillin-sensitive Staphylococcus aureus (MSSA), and vancomycin-resistant Staphylococcus aureus (VRSA) revealed that cyclic heptapeptide Ala6 shown the strongest activity (minimum inhibitory concentration (MIC), 22.1-39.5 µg/mL), comparable to moxifloxacin, followed by cyclic heptapeptide Gly6 (moderate activity) and Tyr6 (least activity). Time-kill assays showed that cyclic heptapeptide Ala6 achieved up to 89.9% colony-forming unit (CFU) reduction in MSSA at 4 × MIC within 5 h. Hemolysis testing confirmed cyclic heptapeptide Ala6's excellent biocompatibility ( 9.3% at 10 µg/mL), while moxifloxacin caused minimal hemolysis. The best peptide was further…
Read the paper
Related studies
- Synthesis, In Vitro and In Silico Molecular Docking Studies of Novel Phthalimide–Pyrimidine Hybrid Analogues to Thalidomide as Potent Antitubercular Agents
- Exploring the inhibitory performance of expired moxifloxacin and norfloxacin on copper corrosion in saline environment
- Molecular investigation of antimicrobial peptides against Helicobacter pylori proteins using a peptide-protein docking approach
- Screening of novel narrow-spectrum benzofuroxan derivatives for the treatment of multidrug-resistant tuberculosis through in silico, in vitro, and in vivo approaches
- Synthesis, Characterization, Anticancer, Antioxidant, and In Silico Evaluation of Semicarbazides and Thiosemicarbazides
- Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.