Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 26, Issue 11, Pages 3060-3064Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2018.02.028
Keywords
Bioconjugation; Cysteine alkylation; Electrophilic handle; Protein engineering; Selective labelling
Funding
- Cambridge Trust
- China Scholarship Council
- EU (Marie-Sklodowska Curie ITN Protein Conjugates)
- EU (Marie Sklodowska-Curie IEF)
- FCT Portugal
- EPSRC
- European Research Council
- EPSRC [EP/M003647/1] Funding Source: UKRI
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Site-selective protein modification strategies can be used to insert non-natural functional groups into protein structures. Herein, we report on the use of the bis-electrophile 3-bromo-2-bromomethyl-1 -propene as a reagent to introduce an electrophilic handle at cysteine residues under mild conditions. This method is demonstrated on a variety of proteins containing a solvent-exposed cysteine residue, including an anti-HER2 nanobody. Chemically distinct protein conjugates are then efficiently formed through further reaction of the electrophilic site with various nucleophiles, including thiols and amines. The resulting chemically-defined conjugates are highly stable in the presence of glutathione or human plasma and retain both the structure and function of the native protein. (C) 2018 The Authors. Published by Elsevier Ltd.
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