Design of thiol-containing amino acids for native chemical ligation at non-Cys sites

Protein chemical synthesis usually relies on the use of native chemical ligation that couples peptide thioester with a Cys-peptide. A limitation of this method is the difficulty of finding an appropriate Cys ligation site in many synthetic targets. To overcome this problem, the ligation desulfurization approach has been developed. This approach involves the use of a thiol-containing amino acid as the ligation partner. After the sequence assembly is completed, the thiol group is removed through a desulfurization reaction to generate the standard amino acids. Currently this strategy has been applied to the ligations at a number of amino acids including Ala, Phe, Val, Lys, Thr, Leu, Pro and Gin. The present article reviews the design and synthesis of these thiol-containing amino acids for native chemical ligation at non-Cys sites. (C) 2013 Lei Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.