title: On resin amino acid side chain attachment strategy for the head to tail synthesis of new glutamine containing gramicidin-S analogs and their antimicrobial activity.
abstract: The alarming increase in infections caused by multiple drug resistant bacteria including methicillin-resistant Staphylococcus aureus has prompted a desperate search for new antimicrobials. Augmenting the discoveries of completely new scaffolds with antimicrobial activity are efforts aimed at modifying existing molecules to optimize activity or reduce toxicity. We report herein the parallel solid-phase synthesis of analogues of the cationic antimicrobial peptide gramicidin S (GS) using amino acid side chain attachment strategy. The ornithine (Orn) residues were replaced by glutamine (Gln) and the aromatic D-phenylalanine (Phe) were replaced by different aromatic D-amino acids. Additional Gln containing GS analogues with all the possible combinations of the hydrophobic amino acids valine and leucine were also synthesized. In this work we also report the antibacterial activity of these analogs against several clinically-important drug-resistant Gram-positive and Gram-negative pathogens.
authors.affiliation: Laboratoire de Pharmacognosie, Faculté de Pharmacie, Rue Avicenne, 5000 Monastir, Tunisia.
authors.forename: Safa
authors.initials: S
authors.lastname: Derbal
authors.forename: Mary
authors.initials: M
authors.lastname: Hensler
authors.forename: Weiqin
authors.initials: W
authors.lastname: Fang
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: Kamel
authors.initials: K
authors.lastname: Ghedira
authors.forename: Adel
authors.initials: A
authors.lastname: Nefzi
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005973:Glutamine / Q000737:chemistry*; D006096:Gramicidin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009952:Ornithine / Q000737:chemistry; D012117:Resins, Synthetic / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D012117:Resins, Synthetic; D005973:Glutamine; D006096:Gramicidin; D009952:Ornithine
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