Artificial lantipeptides from in vitro translations

摘要

We have devised a protocol for enzyme-free insertion of dehydroalanine, dehydrobutyrine and thioether crosslinks into translated peptides. In vitro translation using 4-selenalysine and 4-selenoisoleucine as substitutes for lysine and isoleucine yields peptides that can be converted to polycyclic structures using mild chemistry in water. This methodology presents a gateway for exploring the potential of artificial lantipeptides as scaffolds for drug development. Many gram-positive bacteria secrete highly modified peptides containing dehydroamino acids and thioether crosslinks (lanthionines). The maturation of these compounds (lantipeptides) requires enzymatic post-translational dehydration of β-hydroxy amino acids and formation of lanthionines by Michael-type