The Development of 2^nd Generation of Selenazolidines for Protein Synthesis

Selenocysteine (Sec or U) is the 21^st encoded amino acid, which is found in the active site of many selenoproteins. Recently, this amino acid has found utility in the synthesis of peptides and proteins.¹ Just like Cys, Sec has been used effectively in native chemical ligation (NCL), an important technology for the chemical protein synthesis. During a sequential synthetic progress, the middle peptide segment should contain both N-terminal Cys and C-terminal thioester, and thiazolidine (Thz) is a powerful protecting group that prevents cyclization. Recently, our group explored the utility of the selenazolidine (Sez) as a protected form of Sec for the synthesis of challenging proteins.² Sez-peptide could be converted in to Sec-peptide by MeONH₂ treatment, however, the results showed a slightly slower Sez opening (6 h) than Thz opening (2 h), therefore we herein developed a second-generation substituted selenazolidine variants for chemical protein synthesis (Fig. 1). We will explore the utility of these variants in the synthesis of peptides, proteins and cyclic peptides (Scheme 1).

Fig. 1. Structures of substituted selenazolidines evaluated

Scheme 1. The 2^nd Generation of selenazolidines for Protein Synthesis

References

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