Racemization of Cysteine and Histidine Residues in Automated Peptide Synthesis

摘要

Automated peptide synthesis allows for preparation of a large number of peptide sequences in a fairly straightforward manner. Currently, the most widely applied methodologies utilize Fmocprotection in combination with uromum/phosphonium activating agents for synthesis of peptides. While these new and powerful activating agents can be applied to the majority of commonly used Fmoc amino acids, there are some exceptions such as cysteine and histidine. Racemization of these amino acids during activation with above listed reagents is well documented [1]. Herein we reevaluate the degree of racemization of cysteine and histidine residues using several popular currently available activating agents applied to a typical automated peptide synthesis using an in-situ activation method. Two modified model peptides [le,lg] Z-Ile-Cys(Trt)-Pro-OH and Z-Ile-His-Pro-OH were used as a targets. HPLC analysis was used to evaluate the extent of racemization during cysteine and histidine incorporation.