A thioester ligation approach to amphipathic bicyclic peptide library

Area of Science:

• Peptide Chemistry
• Organic Synthesis
• Biochemistry

Background:

• Bicyclic peptides offer unique structural and functional properties.
• Current synthesis methods often require protected amino acids, limiting efficiency.
• Developing efficient strategies for diverse bicyclic peptide libraries is crucial.

Purpose of the Study:

• To develop an efficient and versatile method for synthesizing amphipathic bicyclic peptide libraries.
• To utilize unprotected peptides to streamline the synthesis process.
• To demonstrate the utility of on-resin and off-resin ligation strategies.

Main Methods:

• On-resin intramolecular thioester ligation of unprotected peptides.
• Off-resin dimethyl sulfoxide (DMSO)-mediated disulfide bond formation.
• Library synthesis approach for generating diverse amphipathic bicyclic peptides.

Main Results:

• Successful synthesis of an amphipathic bicyclic peptide library from unprotected peptide precursors.
• Demonstration of efficient thioester ligation and disulfide bond formation.
• The method allows for the generation of diverse bicyclic peptide structures.

Conclusions:

• The developed method provides an efficient route to amphipathic bicyclic peptides.
• This strategy simplifies peptide synthesis by avoiding protecting groups.
• The approach is suitable for generating diverse libraries for various applications.