Epimer

Peptide

Biology

Native chemical ligation

Biochemistry

Computational biology

Drug discovery

Nanotechnology

In vitro

Cyclic peptide

Chemical synthesis

Chemistry

Materials science

Peptide synthesis

Combinatorial chemistry

Stereochemistry

Chemical Reviews

Cyclic peptides have been attracting a lot of attention in recent decades, especially in the area of drug discovery, as more and more naturally occurring cyclic peptides with diverse biological activities have been discovered. Chemical synthesis of cyclic peptides is essential when studying their structure–activity relationships. Conventional peptide cyclization methods via direct coupling have inherent limitations, like the susceptibility to epimerization at the C-terminus, poor solubility of fully protected peptide precursors, and low yield caused by oligomerization. In this regard, chemoselective ligation-mediated cyclization methods have emerged as effective strategies for cyclic peptide synthesis. The toolbox for cyclic peptide synthesis has been expanded substantially in the past two decades, allowing more efficient synthesis of cyclic peptides with various scaffolds and modifications. This Review will explore different chemoselective ligation technologies used for cyclic peptide synthesis that generate...

Ligation Technologies for the Synthesis of Cyclic Peptides