Synthesis of the lantibiotic lactocin S using peptide cyclizations on solid phase.
Lactocin S is a lantibiotic peptide with potent antibacterial activity against a range of gram-positive bacteria. Because of challenges in obtaining sufficient quantities of this compound from natural sources, the stereochemistry of the lanthionine residues in lactocin S had not been confirmed. This report describes the chemical synthesis of lactocin S on chlorotrityl polystyrene resin in 10% overall yield using intramolecular cyclization to form the lanthionine rings and employing fragment coupling for the two N-terminal residues. This represents the first report of solid-supported synthesis of a naturally occurring lantibiotic. Comparison to lactocin S isolated from Lactobacillus sakei L45 using a combination of HPLC, MS/MS sequencing, bacterial testing, and chiral GC-MS analysis confirmed the initially proposed structure and the stereochemistry of the DL-lanthionine residues.
Ross
Avena C
AC
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
Liu
Hongqiang
H
Pattabiraman
Vijaya R
VR
Vederas
John C
JC
D001430:Bacteriocins; D003500:Cyclization; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D001430:Bacteriocins; D010455:Peptides; C103925:lactocin S