Abstract
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.
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This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2015R1D1A1A01060265).
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Luong, H.X., Kim, DH., Lee, BJ. et al. Antimicrobial activity and stability of stapled helices of polybia-MP1. Arch. Pharm. Res. 40, 1414–1419 (2017). https://doi.org/10.1007/s12272-017-0963-5
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DOI: https://doi.org/10.1007/s12272-017-0963-5