Methods for converting cysteine to dehydroalanine on peptides and proteins (original) (raw)

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* Corresponding authors

a Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford, United Kingdom
E-mail: ben.davis@chem.ox.ac.uk
Fax: +44 (0) 1865 285002
Tel: +44 (0) 1865 275652

b UCB Celltech, 208 Bath Road, Slough, Berkshire, United Kingdom

Abstract

Dehydroalanine is a synthetic precursor to a wide array of protein modifications. We describe multiple methods for the chemical conversion of cysteine to dehydroalanine on peptides and proteins. The scope and limitations of these methods were investigated with attention paid to side reactions, scale, and aqueous- and bio-compatibility. The most general method investigated—a bis-alkylation–elimination of cysteine to dehydroalanine—was applied successfully to multiple proteins and enabled the site-selective synthesis of a glycosylated antibody.

Graphical abstract: Methods for converting cysteine to dehydroalanine on peptides and proteins

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Article information

DOI

https://doi.org/10.1039/C1SC00185J

Article type

Edge Article

Submitted

24 Mar 2011

Accepted

18 May 2011

First published

07 Jun 2011

Download Citation

Chem. Sci., 2011,2, 1666-1676

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Methods for converting cysteine to dehydroalanine on peptides and proteins

J. M. Chalker, S. B. Gunnoo, O. Boutureira, S. C. Gerstberger, M. Fernández-González, G. J. L. Bernardes, L. Griffin, H. Hailu, C. J. Schofield and B. G. Davis,Chem. Sci., 2011, 2, 1666DOI: 10.1039/C1SC00185J

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