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  • Title: Lipidated α/α-AA heterogeneous peptides as antimicrobial agents.
    Author: Singh S, Nimmagadda A, Su M, Wang M, Teng P, Cai J.
    Journal: Eur J Med Chem; 2018 Jul 15; 155():398-405. PubMed ID: 29906686.
    Abstract:
    With an increase of resistance in bacteria there is an urgent need for alternative treatment methods that could complement conventional antibiotics. In the past two decades, focus has been drawn to Host Defense Peptides (HDPs) as potential antibiotic agents. Herein we reported our studies on the development of lipidated α/α-AA heterogeneous peptides as a new class of HDP mimetics. These compounds showed potent antimicrobial activity toward both Gram-positive and Gram-negative bacteria, and they also displayed excellent selectivity as they only exhibited limited hemolytic activity. The fluorescence microscopy suggested that the mechanism of action of these heterogeneous peptides is bacterial membrane disruption, which is believed to be the major reason why it is difficult for bacteria to develop resistance. The subsequent time kill studies suggested that these compounds could rapidly eradicate bacteria. Moreover, this class of compounds could also effectively clear biofilms formed by both Gram-positive and Gram-negative bacteria. These findings suggested that lipidated α/α-AA heterogeneous peptides, as a new class of peptidomimetics, are promising antibiotic agents combating antibiotic resistance.
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