Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, Jammu and Kashmir, India.
Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India.
J Antibiot (Tokyo). 2024 Dec;77(12):794-801. doi: 10.1038/s41429-024-00773-9. Epub 2024 Oct 29.
The incorporation of β-amino acids into peptides is a promising approach to develop proteolytically stable therapeutic agents. Short α/β hybrid peptides containing tBu-βAccː HN-Lys-tBu-βAcc-PEA, P1; HN-Orn-tBu-βAcc-PEA, P2; HN-Arg-tBu-βAcc-PEA, P3; LA-Lys-tBu-βAcc-PEA, P4; LA-Orn-tBu-βAcc-PEA, P5; LA-Arg-tBu-βAcc-PEA, P6; LA-Lys-tBu-βAcc-PEA, P7; LA-Orn-tBu-βAcc-PEA, P8; and LA-Arg-tBu-βAcc-PEA, P9 were prepared. The antimicrobial efficacies of all the peptides were evaluated against ESKAPE pathogens, along with a small panel of multi-drug resistant (MDR) clinical isolates of S. aureus. Among all the peptides, P4, P6, and P7 showed significant efficacies against P. aeruginosa, S. aureus, and MRSA with an MIC value ranging from 6.25 to 12.5 μM. Further, in vitro, anti-staphylococcal assessment with their antimicrobial synergy of the peptides P4, P6, and P7 was carried out against MRSA, due to its better efficacy. The peptides P6 and P7 exhibited MRSA biofilm inhibition of 70% and 77%, respectively, at 4×MIC concentration. At its MIC concentration, about 19% hemolysis was observed for P4, P6, and P7.
将β-氨基酸掺入肽中是开发蛋白水解稳定的治疗剂的一种很有前途的方法。含有 tBu-βAcc∶HN-Lys-tBu-βAcc-PEA、P1；HN-Orn-tBu-βAcc-PEA、P2；HN-Arg-tBu-βAcc-PEA、P3；LA-Lys-tBu-βAcc-PEA、P4；LA-Orn-tBu-βAcc-PEA、P5；LA-Arg-tBu-βAcc-PEA、P6；LA-Lys-tBu-βAcc-PEA、P7；LA-Orn-tBu-βAcc-PEA、P8 和 LA-Arg-tBu-βAcc-PEA、P9 的短 α/β 杂合肽被制备。所有肽的抗微生物功效均针对 ESKAPE 病原体以及一小部分多药耐药（MDR）金黄色葡萄球菌临床分离株进行了评估。在所有肽中，P4、P6 和 P7 对铜绿假单胞菌、金黄色葡萄球菌和 MRSA 表现出显著的功效，MIC 值范围为 6.25 至 12.5 μM。此外，由于其更好的功效，在体外对其抗金黄色葡萄球菌的评估中，用这些肽 P4、P6 和 P7 进行了抗菌协同作用的研究。肽 P6 和 P7 分别在 4×MIC 浓度下对 MRSA 生物膜抑制率达到 70%和 77%。在其 MIC 浓度下，P4、P6 和 P7 观察到约 19%的溶血。
