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Synthesis, biological activity and solution structure of new analogues of the antimicrobial Gramicidin S
Author(s) -
Kamysz Elżbieta,
Mickiewicz Beata,
Kamysz Wojciech,
Bielińska Sylwia,
RodziewiczMotowidło Sylwia,
Ciarkowski Jerzy
Publication year - 2011
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1314
Subject(s) - gramicidin s , chemistry , antiparallel (mathematics) , gramicidin , antimicrobial , peptide , stereochemistry , antimicrobial peptides , amino acid , combinatorial chemistry , amino acid residue , biochemistry , peptide sequence , organic chemistry , membrane , physics , quantum mechanics , magnetic field , gene
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.