Rapid Additive-Free Selenocystine–Selenoester Peptide Ligation
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Open Access
Type
ArticleAuthor/s
Mitchell, Nicholas J.Malins, Lara R.
Liu, Xuyu
Thompson, Robert E.
Chan, Bun
Radom, Leo
Payne, Richard J.
Abstract
We describe an unprecedented reaction between peptide selenoesters and peptide dimers bearing N-terminal selenocystine that proceeds in aqueous buffer to afford native amide bonds without the use of additives. The selenocystine-selenoester ligations are complete in minutes, even at sterically hindered junctions, and can be used in concert with one-pot deselenization chemistry. Various pathways for the transformation are proposed and probed through a combination of experimental and computational studies. Our new reaction manifold is also showcased in the total synthesis of two proteins.We describe an unprecedented reaction between peptide selenoesters and peptide dimers bearing N-terminal selenocystine that proceeds in aqueous buffer to afford native amide bonds without the use of additives. The selenocystine-selenoester ligations are complete in minutes, even at sterically hindered junctions, and can be used in concert with one-pot deselenization chemistry. Various pathways for the transformation are proposed and probed through a combination of experimental and computational studies. Our new reaction manifold is also showcased in the total synthesis of two proteins.
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Date
2015-10-21Publisher
American Chemical SocietyCitation
Nicholas J. Mitchell, Lara R. Malins, Xuyu Liu, Robert E. Thompson, Bun Chan, Leo Radom, and Richard J. Payne Journal of the American Chemical Society 2015 137 (44), 14011-14014 DOI: 10.1021/jacs.5b07237Share