College of Pharmacy, Dongguk University, Seoul, 100-715, Korea.
College of Pharmacy, Seoul National University, Seoul, 151-742, Korea.
Arch Pharm Res. 2017 Dec;40(12):1414-1419. doi: 10.1007/s12272-017-0963-5. Epub 2017 Oct 26.
Polybia-MP1 is a well-known natural antimicrobial peptide isolated from the venom of the social wasp Polybia paulista. A recent study showed that this peptide displays a broad antibacterial spectrum as well as low toxicity to human red blood cells and normal fibroblasts. However, its moderate antimicrobial activity and high susceptibility to protease have been a major hurdle for clinical use. This study examined the possibility of developing biologically more potent, yet metabolically more stable, analogues of MP1 using an emerging technology termed "all-hydrocarbon stapling." The stapled analogues of MP1 showed more than a threefold increase in helicity as well as an approximately 70-fold enhancement in proteolytic stability. These stapled analogues also exhibited a significant increase in inhibition against some Gram-positive bacteria while displaying a modest enhancement in hemolytic activity. Overall, the current study demonstrated that the all-hydrocarbon stapling system is a highly useful tool for the development of biologically more potent and metabolically more stable analogues of natural antimicrobial peptides.
聚多杀菌素-MP1 是一种从社会性黄蜂 Polybia paulista 的毒液中分离出来的著名天然抗菌肽。最近的一项研究表明，该肽具有广谱的抗菌谱，对人红细胞和正常成纤维细胞的毒性较低。然而，其中等的抗菌活性和对蛋白酶的高敏感性一直是临床应用的主要障碍。本研究利用一种新兴的技术，即“全碳氢化合物订书钉”，研究了开发具有更强生物学活性、代谢更稳定的 MP1 类似物的可能性。与 MP1 的订书钉类似物相比，其螺旋度增加了三倍以上，对蛋白水解的稳定性提高了约 70 倍。这些订书钉类似物对一些革兰氏阳性菌的抑制作用也显著增加，同时溶血活性略有增强。总的来说，本研究表明，全碳氢化合物订书钉系统是开发具有更强生物学活性和代谢更稳定的天然抗菌肽类似物的非常有用的工具。
