Huang, S.; Su, G.; Jiang, S.; Chen, L.; Huang, J.; Yang, F. New N-Terminal Fatty-Acid-Modified Melittin Analogs with Potent Biological Activity. Int. J. Mol. Sci.2024, 25, 867.
Huang, S.; Su, G.; Jiang, S.; Chen, L.; Huang, J.; Yang, F. New N-Terminal Fatty-Acid-Modified Melittin Analogs with Potent Biological Activity. Int. J. Mol. Sci. 2024, 25, 867.
Huang, S.; Su, G.; Jiang, S.; Chen, L.; Huang, J.; Yang, F. New N-Terminal Fatty-Acid-Modified Melittin Analogs with Potent Biological Activity. Int. J. Mol. Sci.2024, 25, 867.
Huang, S.; Su, G.; Jiang, S.; Chen, L.; Huang, J.; Yang, F. New N-Terminal Fatty-Acid-Modified Melittin Analogs with Potent Biological Activity. Int. J. Mol. Sci. 2024, 25, 867.
Abstract
Melittin, a natural antimicrobial peptide, displays a broad-spectrum antimicrobial activity, which has caused increasing attention as a potential antibiotic alternative. However, melittin has not been used widely at present due to its high hemolysis and low proteolytic stability. In this study, N-terminal fatty acid was conjugated to melittin to develop new melittin-derived lipopep-tides (MDLs) for improving the limitation of melittin. Our results showed that, the antimicrobial activity of MDLs was increased by 2 to 16 times compared with native melittin, and the stability of these MDLs against trypsin and pepsin degradation was increased by 50 to 80%. Besides, the hemolytic of the MDLs decreased when the length of the carbon chain of fatty acids exceeded 10. Among them, the newly designed analog Mel-C8 showed optimal antimicrobial activity and protease stability. The antimicrobial mechanism studied revealed that the MDLs showed a rapid bactericidal effect by interacting with LPS or LTA and penetrating the bacterial cell membrane. In conclusion, we designed and synthesized a new class of MDLs with potent antimicrobial activity, high proteolytic stability, and low hemolysis through N-terminal fatty acid conjugation.
Biology and Life Sciences, Biochemistry and Molecular Biology
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