Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
The adaptation of native chemical ligation to protein semisynthesis has become a powerful way to address problems in the analysis of protein structure and function. In particular, the exploitation of nature's inteins in expressed protein ligation is now a standard approach in the study of proteins. Site-specific incorporation of unnatural amino acids, biophysical probes and post-translational modifications in proteins have led to new insights into enzyme mechanisms, protein folding, ion channel function, translation and signaling.