Abstract

Lariat or lasso peptides are a structurally uniquefamily of ribosomally synthesized bioactive peptides producedby microbes. They range from 16 to 21 residues in size andare characterized by a post-translational modification inthe form of a lactam bond between a conserved asparticor glutamic acid and the peptide N-terminus, resulting inan 8 or 9 residue macrocycle, which is threaded by theC-terminal part of the peptide chain. This noose-like featureresults in unique properties, including remarkable chemicaland biological stability, suggesting that this bacterial ropetrick may well provide an ideal new framework for the designof peptide based pharmaceuticals.