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• W2617435406 abstract "Abstract Cathelicidins are regarded as promising antibiotics due to their capability against antibiotic-resistant bacteria without cytotoxicity. However, some concerns about the balance of cytotoxicity and antimicrobial activity, weak stability and enzymatic susceptibility sually restrict their therapeutic use. Here, we designed a series of shortened variants, Hc1~15, based on our previously characterized Hc-CATH. Hc3, the one with the best activity, after point mutation was engineered with a trypsin inhibitor loop, ORB-C, to obtain four hybrid peptides: H3TI, TIH3, H3TIF and TIH3F. All four except TIH3 were found possessing an appreciable profile of proteases inhibitory and antimicrobial characteristics without increase in cytotoxicity. Among them, TIH3F exhibited the most potent and broad-spectrum antimicrobial and anti-inflammatory activities. Fluorescence spectroscopy has demonstrated a quick induction of bacterial membrane permeability by TIH3F leading to the cell death, which also accounts for its fast anti-biofilm activity. Such mode of antimicrobial action was mainly attributed to peptides’ amphiphilic and helical structures determined by CD and homology modeling. Besides, TIH3F exhibited good tolerance to salt, serum, pH, and temperature, indicating a much better physiological stability in vitro than Hc3, Most importantly, in the case of resistance against proteases hydrolysis, current hybrid peptides displayed a remarkable enhancement than their original templates." @default.
• W2617435406 created "2017-06-05" @default.
• W2617435406 creator A5013038112 @default.
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• W2617435406 date "2017-06-01" @default.
• W2617435406 modified "2023-09-28" @default.
• W2617435406 title "Cathelicidin-trypsin inhibitor loop conjugate represents a promising antibiotic candidate with protease stability" @default.
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• W2617435406 doi "https://doi.org/10.1038/s41598-017-02050-2" @default.
• W2617435406 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5453931" @default.
• W2617435406 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28572668" @default.
• W2617435406 hasPublicationYear "2017" @default.
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