Biomimetic synthesis of lantibiotics.
The lantibiotics are a class of highly posttranslationally modified small peptide antibiotics containing numerous lanthionine and dehydroamino acid residues. We have prepared peptides containing multiple dehydroamino acids and cysteine residues in order to probe the biomimetic synthesis of the lantibiotics from their precursor peptides. A novel synthetic methodology was developed to allow the synthesis of multiple dehydroamino acid containing peptides. Cyclisations were rapid, quantitative and regiospecific. Remarkably the peptide sequences alone appear to contain sufficient information to direct a series of stereo- and regiospecific ring closures. Thus both the two linear peptides for the B and E-rings closed stereoselectively. In the case of the A-ring precursor peptide which contained two dehydroamino acids, cyclisation was again totally regioselective, although not totally stereoselective.
Burrage
S
S
Department of Chemistry, Southampton University, Highfield, UK.
Raynham
T
T
Williams
G
G
Essex
J W
JW
Allen
C
C
Cardno
M
M
Swali
V
V
Bradley
M
M
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010455:Peptides; D013440:Sulfides
D000900:Anti-Bacterial Agents; D010455:Peptides; D013440:Sulfides; C001520:lanthionine; D000409:Alanine