Accessing posttranslationally modified proteins through thiol positioning

The field of peptide synthesis achieved considerable advancement in the last decade with the discovery of native chemical ligation (NCL). With the aim of broader application of ligation methods in the synthesis of proteins several strategies have been developed. One of the significant contributions to NCL based strategies is the desulfurization reaction, which removes the thiol handle to generate the unmodified protein. The principle of NCL coupled with desulfurization is effortlessly executed in the synthesis of posttranslationally modified proteins. This short account will cover the recent developments on how new methods of chemical ligation is being evolved and exploited in achieving posttranslationally modified proteins. New ligation methods are presented which allow the total chemical synthesis of posttranslationally modified proteins. The success of these ligation strategies revolved around positioning of a sufhydryl functionality at a suitable position in a peptide to capture a thioester peptide for an amide bond formation.