Bioengineering and functional characterization of arenicin shortened analogs with enhanced antibacterial activity and cell selectivity

Journal of Peptide Science : an Official Publication of the European Peptide Society
Pavel V PanteleevTatiana V Ovchinnikova

Abstract

New bioengineering approaches are required for development of more active and less toxic antimicrobial peptides. In this study we used β-hairpin antimicrobial peptide arenicin-1 as a template for design of more potent antimicrobials. In particular, six shortened 17-residue analogs were obtained by recombinant expression in Escherichia coli. Besides, we have introduced the second disulfide bridge by analogy with the structure of tachyplesins. As a result, a number of analogs with enhanced activity and cell selectivity were developed. In comparison with arenicin-1, which acts on cell membranes with low selectivity, the most potent and promising its analog termed ALP1 possessed two-fold higher antibacterial activity and did not affect viability of mammalian cells at concentration up to 50 μM. The therapeutic index of ALP1 against both Gram-positive and Gram-negative bacteria was significantly increased compared with that of arenicin-1 while the mechanism of action remained the same. Like arenicin-1, the analog rapidly disrupt membranes of both stationary and exponential phase bacterial cells and effectively kills multidrug-resistant Gram-negative bacteria. Furthermore, ALP1 was shown to bind DNA in vitro at a ratio of 1:1 (w/w). T...Continue Reading

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Citations

Aug 18, 2017·Chemical Biology & Drug Design·Denis V KuzminTatiana V Ovchinnikova
Sep 1, 2019·Marine Drugs·Renato BrunoAurélie Tasiemski
Dec 18, 2018·Frontiers in Microbiology·Pavel V PanteleevTatiana V Ovchinnikova
Dec 6, 2018·Marine Drugs·Ekaterina S UmnyakovaMikhail N Berlov
Nov 30, 2018·Marine Drugs·Mariana B MarggrafTatiana V Ovchinnikova
Apr 22, 2017·Bulletin of Experimental Biology and Medicine·D V KuzminT V Ovchinnikova

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