Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-180001, India.
Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-180001 India; Academy of Scientific and Innovative Research, New Delhi, India.
Peptides. 2017 Nov;97:46-53. doi: 10.1016/j.peptides.2017.09.016. Epub 2017 Sep 28.
The peptides containing β- and γ-amino acids, LA-Lys-PEA, P1; LA-Lys-β-Acc-PEA, P2; LA-Orn-β-Acc-PEA, P3; LA-Lys-Gpn-PEA, P4; LA-Orn-Gpn-PEA, P5; LA-Lys-γ-Phe-PEA, P6, LA-γ-Leu-Lys-PEA, P7 and LA-β-Pip(Ac)-Lys-PEA, P8 were synthesized, characterized and evaluated against Gram-positive and Gram-negative bacteria. Among all, peptides P2, P3, P4 and P5 exhibited potent activity (MIC 6.25μM) against S. aureus MTCC 737 and P. aeruginosa MTCC 424. In order to understand the efficacy of peptides and mechanism of action, time kill kinetics and fluorescence microscopic studies were performed against S. aureus and P. aeruginosa for the peptides P2, P3, P4 and P5. P4 took half time to show the bactericidal effect on P. aeruginosa and S. aureus in comparison to P2 at their 2x MICs. Fluorescence microscopic studies suggested that peptides P2 and P4 both killed the bacteria via membrane disruption. Further, P4 exhibited lowest haemolytic activity among active peptides and negligible cytotoxic activity against human cancer cell lines A-549, PC-3 and HCT-116 at its MIC.
合成并表征了含有β-和γ-氨基酸的肽 LA-Lys-PEA、P1；LA-Lys-β-Acc-PEA、P2；LA-Orn-β-Acc-PEA、P3；LA-Lys-Gpn-PEA、P4；LA-Orn-Gpn-PEA、P5；LA-Lys-γ-Phe-PEA、P6、LA-γ-Leu-Lys-PEA、P7 和 LA-β-Pip(Ac)-Lys-PEA、P8，并对其进行了革兰氏阳性菌和革兰氏阴性菌的活性评价。其中，肽 P2、P3、P4 和 P5 对金黄色葡萄球菌 MTCC 737 和铜绿假单胞菌 MTCC 424 表现出很强的活性（MIC 为 6.25μM）。为了了解肽的功效和作用机制，对 P2、P3、P4 和 P5 进行了针对金黄色葡萄球菌和铜绿假单胞菌的时间杀伤动力学和荧光显微镜研究。与 P2 相比，P4 在其 2x MIC 时对铜绿假单胞菌和金黄色葡萄球菌表现出半时间的杀菌效果。荧光显微镜研究表明，肽 P2 和 P4 均通过破坏细胞膜来杀死细菌。此外，P4 在其 MIC 下对人癌细胞系 A-549、PC-3 和 HCT-116 表现出最低的溶血活性和可忽略的细胞毒性。
