The Bogorol family of antibiotics: template-based structure elucidation and a new approach to positioning enantiomeric pairs of amino acids.
The sequence positions of d and l Leu and Lys residues in bogorol A (1) have been defined by a simple and novel approach that utilizes small amounts of sample and focuses on detecting the order in which amino acids are liberated from the parent peptide during acid-catalyzed hydrolysis. This technique builds on a previously established relationship between the steric and electronic features of amino acids and their predilection for acidic liberation from polypeptides via dipeptides. The results, which complete the structure of bogorol A, have been confirmed by traditional degradation experiments. Utilizing the knowledge of the structure of bogorol A (1) as a template, we rapidly elucidated the structures of bogorols B-E (2-5) via analysis of ESI-MS and ESI-MS/MS data and GC analysis of degradation products. The bogorol cationic peptide antibiotics contain a number of unusual structural features, which include the reduction of the C-terminal residue to valinol, an N-terminal residue of 2-hydroxy-3-methylpentanoic acid, the incorporation of four d amino acids, and the presence of a dehydroamino acid. Bogorols show selective and relatively potent activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp., as well as moderate activity against Escherichia coli.
Barsby
Todd
T
Department of Chemistry, University of British Columbia (UBC), 2036 Main Mall, Vancouver, British Columbia, V6T 1Z1, Canada.
Warabi
Kaoru
K
Sørensen
Dan
D
Zimmerman
William T
WT
Kelly
Michael T
MT
Andersen
Raymond J
RJ
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification* / Q000494:pharmacology*; D001407:Bacillus / Q000737:chemistry; D006868:Hydrolysis; D050296:Microbial Viability / Q000187:drug effects; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D053719:Tandem Mass Spectrometry
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D010455:Peptides