Disulfide Formation Strategies in Peptide Synthesis

Disulfide bonds play an important role in both proteins and peptides. They cause conformational constraints and increase the stability of such molecules. In nature, disulfide bonds are very common in animal and plant peptide toxins. These disulfide‐rich peptides typically bind very selectively with high affinities to their targets. Disulfide‐rich peptides are of great importance as potential therapeutics. Robust, convenient, and efficient methods are needed in order to prepare disulfide‐rich peptides to facilitate the drug discovery process. This microreview explores new cysteine protecting groups that replace obsolete protecting groups, reduce racemization, or facilitate regioselective disulfide formation, new disulfide formation strategies to assist in the synthesis of complex disulfide‐rich peptides, and the use of selenocysteine to direct disulfide formation. Disulfide bonds are important structural features of peptides and proteins. The synthesis of complex disulfide‐rich peptides is time‐consuming and challenging. New disulfide formation strategies are required, and these are under constant development. Here we examine new cysteine protecting groups and disulfide formation strategies from 2006 until now.