Artificial lantipeptides from in vitro translations

Area of Science:

• Biochemistry
• Synthetic Chemistry
• Drug Discovery

Background:

• Lantipeptides are a class of ribosomally synthesized and post-translationally modified peptides with complex crosslinking.
• Current methods for synthesizing modified peptides often involve complex enzymatic or chemical steps.
• Artificial lantipeptides offer potential as novel scaffolds for therapeutic agents.

Purpose of the Study:

• To develop an efficient and enzyme-free protocol for incorporating dehydroamino acids and thioether crosslinks into translated peptides.
• To explore the use of non-canonical amino acids in in vitro translation for generating complex peptide structures.
• To establish a foundation for the development of artificial lantipeptides as drug development scaffolds.

Main Methods:

• Enzyme-free insertion of dehydroalanine, dehydrobutyrine, and thioether crosslinks into peptides.
• In vitro translation utilizing 4-selenalysine and 4-selenoisoleucine as substitutes for lysine and isoleucine.
• Mild aqueous chemistry for the conversion of modified peptides into polycyclic structures.

Main Results:

• Successful implementation of a protocol for enzyme-free peptide crosslinking.
• Generation of peptides containing dehydroalanine, dehydrobutyrine, and thioether linkages.
• Demonstration of mild chemical conversion to polycyclic peptide structures.

Conclusions:

• The developed methodology provides a versatile platform for synthesizing artificial lantipeptides.
• This approach facilitates the exploration of novel peptide-based scaffolds for drug discovery.
• The enzyme-free nature of the protocol simplifies the synthesis of complex modified peptides.