Medicinal Chemistry Division, Council of Scientific & Industrial Research-Indian Institute of Integrative Medicine(CSIR-IIIM), Jammu-180001, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India.
J Antibiot (Tokyo). 2021 Jul;74(7):480-483. doi: 10.1038/s41429-021-00419-0. Epub 2021 Mar 25.
The present work describes the synthesis of hybrid dipeptides H-Lys-Gpn-PEA, C1; H-Lys-βAPEA, C2, and THPA conjugated dipeptides, THPA-Lys-Gpn-PEA, C3, and THPA-Lys-βA-PEA, C4. All the peptides were evaluated against both Gram-negative and Gram-positive bacterial strains. Among all, peptide C4 exhibited the most potent activity with MIC 1.56 μM against P. aeruginosa (MTCC 424) and S. aureus (MTCC 737). Further, time-kill kinetics, fluorescence assays, and scanning electron microscopy (SEM) studies were performed in order to understand the mechanism of action and efficacy of peptide C4, The fluorescence assays and SEM images demonstrated the bacterial killing through membrane disruption. The peptide C4 exhibited very low hemolytic activity with negligible cytotoxicity against normal human breast cell line FR2.
本工作描述了混合二肽 H-Lys-Gpn-PEA（C1）、H-Lys-βAPEA（C2）和 THPA 缀合二肽 THPA-Lys-Gpn-PEA（C3）和 THPA-Lys-βA-PEA（C4）的合成。所有肽均针对革兰氏阴性和革兰氏阳性细菌菌株进行了评估。在所有这些肽中，肽 C4 对铜绿假单胞菌（MTCC 424）和金黄色葡萄球菌（MTCC 737）的 MIC 为 1.56 μM，表现出最强的活性。此外，还进行了时间杀伤动力学、荧光测定和扫描电子显微镜（SEM）研究，以了解肽 C4 的作用机制和功效。荧光测定和 SEM 图像表明，细菌通过破坏细胞膜而被杀死。肽 C4 表现出非常低的溶血活性，对正常人类乳腺细胞系 FR2 的细胞毒性可忽略不计。
