The Synthesis of Active and Stable Diaminopimelate Analogues of the Lantibiotic Peptide Lactocin S
Citations Over TimeTop 10% of 2012 papers
Abstract
Lantibiotic peptides are potent antimicrobial compounds produced by Gram-positive bacteria. They can be used in food preservation, and some also show potential for clinical applications. Unfortunately, some of these peptides can be susceptible to inactivation by oxidation of the sulfur-containing amino acid lanthionine, limiting their use. Here we describe the synthesis and testing of diaminopimelate analogues of the lantibiotic lactocin S. These analogues were designed to improve the oxidative stability of the peptide by replacing the sulfur in lanthionine with a methylene unit. Lanthionine was systematically replaced with diaminopimelate during solid-phase peptide synthesis to produce several analogues. One analogue, A-DAP lactocin S, was found to retain full biological activity in addition to displaying increased stability. This is the first time a synthetic lanthionine ring analogue of a lantibiotic has retained natural activity levels. This methodology is potentially very promising for use in producing more stable, medically relevant lantibiotics.
Related Papers
- → The nisin–lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics(2004)542 cited
- → The lantibiotic nisin, a special case or not?(1999)269 cited
- → Insights into In Vivo Activities of Lantibiotics from Gallidermin and Epidermin Mode-of-Action Studies(2006)167 cited
- Semi-synthesis of nisin-based peptide antibiotics(2013)
- Synthesis and Conformational Studies of the Lipid II-Binding Rings of Nisin and Mutacin I(2018)