title: Synthesis, biological activity and solution structure of new analogues of the antimicrobial Gramicidin S.
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.
authors.affiliation: University of Gdańsk, Faculty of Chemistry, Sobieskiego 18, Gdańsk, 80-952, Poland. kamysz@chem.univ.gda.pl
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Kamysz
authors.forename: Beata
authors.initials: B
authors.lastname: Mickiewicz
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamysz
authors.forename: Sylwia
authors.initials: S
authors.lastname: Bielińska
authors.forename: Sylwia
authors.initials: S
authors.lastname: Rodziewicz-Motowidło
authors.forename: Jerzy
authors.initials: J
authors.lastname: Ciarkowski
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D006096:Gramicidin / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D006096:Gramicidin