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Antimicrobial activity and stability of stapled helices of polybia-MP1

Luong, Huy X., Kim, Do-Hee, Lee, Bong-Jin, Kim, Young-Woo
Archives of pharmacal research 2017 v.40 no.12 pp. 1414-1419
Gram-positive bacteria, Polybia paulista, antibacterial properties, antimicrobial peptides, erythrocytes, fibroblasts, hemolysis, humans, proteinases, proteolysis, social wasps, technology, toxicity, venoms
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.