Synthesis,biological activity and solution structure of new analogues of the antimicrobial Gramicidin S |
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Authors: | Elżbieta Kamysz Beata Mickiewicz Wojciech Kamysz Sylwia Bielińska Sylwia Rodziewicz‐Motowidło Jerzy Ciarkowski |
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Affiliation: | 1. University of Gdańsk, Faculty of Chemistry, Sobieskiego 18, Gdańsk, 80‐952, Poland;2. Medical University of Gdańsk, Faculty of Pharmacy, Al. Gen. J. Hallera 107, Gdańsk, 80‐416, Poland |
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Abstract: | Gramicidin S (GS) is a cyclo‐decapeptide antibiotic isolated from Bacillus brevis. The structural studies have shown that GS forms a two‐stranded antiparallel β‐sheet imposed by two II′ β‐turns. Despite its wide Gram+ and Gram? antimicrobial spectrum, GS is useless in therapy because of its high hemotoxicity in humans. It was found, however, that the analogues of GS‐14 (GS with 14 amino acid residues) attained a better antimicrobial selectivity when their amphipatic moments were perturbed. In this study, we report effects of similar perturbations imposed on GS cyclo‐decapeptide analogues. Having solved their structures by NMR/molecular dynamics and having tested their activities/selectivities, we have concluded that the idea of perturbation of the amphipatic moment does not work for GS‐10_0 analogues. An innovative approach to the synthesis of head‐to‐tail cyclopeptides was used. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. |
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Keywords: | antimicrobial peptide gramicidin S amphipathicity cyclic peptide synthesis NMR molecular dynamics hemolysis structure‐activity relationship |
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