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- W2048245422 abstract "Light-driven reversible conformational changes of proteins are of fundamental importance to nature. Here, we present the development of a photo-controllable antimicrobial peptide (AMP), based on a novel photo-switch in the backbone. AMPs are an essential part of innate immune system of living organisms and defend them against various bacteria, viruses, and fungi. They are promising therapeutic sources for future antibiotics as they permeabilize bacterial membranes, but they tend to suffer from cytotoxic side effects against eukaryotic cells. These problems, preventing clinical applications, could be eliminated by remotely switching the membranolytic activity ON and OFF. We have thus designed and synthesized a reversibly photo-isomerizable amino acid analogue based on a diarylethylene scaffold. The amino acid analogue was incorporated into the cyclic backbone of the antimicrobial peptide Gramicidin S. Several peptidomimetics were successfully synthesized, their photochromic features were recorded in the ON and OFF states, and the corresponding molecular conformations were analyzed by CD spectroscopy and MD simulations. Antimicrobial assays and hemolysis tests showed that the biological activity could be directly controlled by irradiation with visible and UV light. These results open the way to develop new strategies for treating bacterial infections or other localized pathologies, by activating the antibiotic with light only in those specific areas where needed. The use of such ‘smart’ antibiotics will largely eliminate the harmful side effects on the whole body and should also prevent the concomitant development of bacterial resistance." @default.
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- W2048245422 date "2014-01-01" @default.
- W2048245422 modified "2023-09-26" @default.
- W2048245422 title "Switching the Antimicrobial Activity of Gramicidin S by Light" @default.
- W2048245422 doi "https://doi.org/10.1016/j.bpj.2013.11.2490" @default.
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