title: Chemical synthesis and biological activity of analogues of the lantibiotic epilancin 15X.
abstract: Lantibiotics are a large family of antibacterial peptide natural products containing multiple post-translational modifications, including the thioether structures lanthionine and methyllanthionine. Efforts to probe structure-activity relationships and engineer improved pharmacological properties have driven the development of new methods to produce non-natural analogues of these compounds. In this study, solid-supported chemical synthesis was used to produce analogues of the potent lantibiotic epilancin 15X, in order to assess the importance of several N-terminal post-translational modifications for biological activity. Surprisingly, substitution of these moieties, including the unusual N-terminal D-lactyl moiety, resulted in relatively small changes in the antimicrobial activity and pore-forming ability of the peptides.
authors.affiliation: Howard Hughes Medical Institute and Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Knerr
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: van der Donk
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001430:Bacteriocins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D013203:Staphylococcal Infections / Q000188:drug therapy; D013210:Staphylococcus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D010455:Peptides; C500288:epilancin 15X