Antimicrobial activity and stability of stapled helices of polybia-MP1

作者：Luong Huy X; Kim Do Hee; Lee Bong Jin; Kim Young Woo^*

来源：Archives of Pharmacal Research, 2017, 40(12): 1414-1419.

DOI：10.1007/s12272-017-0963-5

• Antimicrobial peptides
• alpha-Helix
• Stapled peptides
• Amphipathic peptides
• Proteolytic resistance

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.

• 出版日期2017-12