Abstract
The use of native chemical ligation at selenocysteine (Sec) residues with peptide thioesters and additive-free selenocystine ligation with peptides bearing phenyl selenoesters, in concert with one-pot oxidative deselenization chemistry, is described. These approaches provide a simple and rapid method for accessing native peptides with serine in place of Sec at the ligation junction. The efficiency of both variants of the one-pot ligation-oxidative deselenization chemistry is probed through the synthesis of a MUC5AC-derived glycopeptide.
Highlights
Native chemical ligation is a chemoselective reaction that enables the fusion of a peptide bearing a C-terminal thioester with a peptide possessing an N-terminal cysteine (Cys) moiety in aqueous media.[1]
In this work we proposed an effective solution to this synthetic bottleneck through the use of the alkyl thiol additive trifluoroethanethiol (TFET), which has been shown to facilitate native chemical ligation reactions at Cys[12] and other thiolderived amino acids[13] at similar rates to the gold standard thiol additives e.g. MPAA
We have described the use of native chemical ligation between Sec-containing peptides and peptide thioesters, coupled with one-pot oxidative deselenization chemistry, to afford native peptides bearing a Ser residue at the ligation junction in place of Sec
Summary
Native chemical ligation is a chemoselective reaction that enables the fusion of a peptide bearing a C-terminal thioester with a peptide possessing an N-terminal cysteine (Cys) moiety in aqueous media.[1]. We explored the effect of an internal Cys residue on the ligation and the oxidative deselenization reaction by preparing peptide 10 (entry 9, Table 1).
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