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  • Title: Artificial beta-defensin based on a minimal defensin template.
    Author: Antcheva N, Morgera F, Creatti L, Vaccari L, Pag U, Pacor S, Shai Y, Sahl HG, Tossi A.
    Journal: Biochem J; 2009 Jul 15; 421(3):435-47. PubMed ID: 19453294.
    Abstract:
    We have designed and chemically synthesized an artificial beta-defensin based on a minimal template derived from the comparative analysis of over 80 naturally occurring sequences. This molecule has the disulfide-bridged beta-sheet core structure of natural beta-defensins and shows a robust salt-sensitive antimicrobial activity against bacteria and yeast, as well as a chemotactic activity against immature dendritic cells. An SAR (structure-activity relationship) study using two truncated fragments or a Cys-->Ser point-mutated analogue, from which one or two of the three disulfide bridges were absent, indicated that altering the structure resulted in a different type of membrane interaction and a switch to different modes of action towards both microbial and host cells, and that covalent dimerization could favour antimicrobial activity. Comparison of the structural, aggregational and biological activities of the artificial defensin with those of three human beta-defensins and their primate orthologues provided useful information on how their mode of action may relate to specific structural features.
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