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. 2015 Aug 12;137(31):9784-7.
doi: 10.1021/jacs.5b05447. Epub 2015 Jul 30.

An Umpolung Approach for the Chemoselective Arylation of Selenocysteine in Unprotected Peptides

Daniel T Cohen  1 , Chi Zhang  1 , Bradley L Pentelute  1 , Stephen L Buchwald  1
Affiliations

An Umpolung Approach for the Chemoselective Arylation of Selenocysteine in Unprotected Peptides

Daniel T Cohen et al. J Am Chem Soc. .

Abstract

Herein we report an umpolung strategy for the bioconjugation of selenocysteine in unprotected peptides. This mild and operationally simple approach takes advantage of the electrophilic character of an oxidized selenocysteine (Se-S bond) to react with a nucleophilic arylboronic acid to provide the arylated selenocysteine within hours. This reaction is amenable to a wide range of boronic acids with different biorelevant functional groups and is unique to selenocysteine. Experimental evidence indicates that under oxidative conditions the arylated derivatives are more stable than the corresponding alkylated selenocysteine.

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Conflict of interest statement

The authors declare the following competing financial interest(s): MIT has filed a provisional patent based on this technology of which S.L.B, B.L.P, D.T.C., and C.Z. will receive possible royalties.

Figures

Figure 1
Figure 1
Bioconjugation of cysteine and selenocysteine.
Figure 2
Figure 2
Stability study of functionalized selenocysteine in peptides. Yields were determined by integration of total ion currents from LC–MS analyses of the unpurified reaction mixtures.
See this image and copyright information in PMC

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