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.
Trimethoxyphenylthio (S-Tmp) is described as a novel cysteine protecting group in Fmoc solid phase peptide synthesis replacing the difficult to remove tert-butylthio. S-Tmp and dimethoxyphenylthio (S-Dmp) were successfully used for cysteine protection in a variety of peptides. Moreover, both groups can be removed in 5 min with mild reducing agents. S-Tmp is recommended for cysteine protection, as it yields crude peptides of high purity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.