Abstract
Native chemical ligation has emerged as a powerful method in peptide synthesis. In this method, an initial transthioesterification step involves a chemoselective reaction that occurs between a peptide fragment containing an amino-terminal cysteine residue and a second peptide fragment containing a carboxyl-terminal thioester group, leading to an S-acyl intermediate. A subsequent S->N acyl migration forms a native amide bond. Of the translatable amino acids, only cysteine has the requisite β-mercapto substituent. However, the method could in principle be extended to other amino acids through the use of a temporary sulfhydryl, which could be removed post-ligation with Ra-Ni. To explore this possibility, we prepared the diastereomeric β-methylcysteines (thiothreonines). The suitability of these reagents for native chemical ligation was discussed, and efforts toward improved and general stereoselective syntheses of β-substituted cysteines was discussed.
Lai, Zhi (2000). Beta-methylcysteines: synthesis and application in native chemical ligation. Master's thesis, Texas A&M University. Available electronically from
https : / /hdl .handle .net /1969 .1 /ETD -TAMU -2000 -THESIS -L353.