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Protein Conjugation by Electrophilic Alkynylation Using 5-(Alkynyl)dibenzothiophenium Triflates.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Laserna, Victor 
Istrate, Alena 
Kafuta, Kevin 

Abstract

5-(Alkynyl)dibenzothiophenium triflates are introduced as new reagents to prepare different protein conjugates through site-selective cysteine alkynylation. The protocol developed allows a highly efficient label of free cysteine-containing proteins with relevant biological roles, such as ubiquitin, the C2A domain of Synaptotagmin-I, or HER2 targeting nanobodies. An electrophilic bis-alkynylating reagent was also designed. The second alkynylating handle thus introduced in the desired protein enables access to protein-thiol, protein-peptide, and protein-protein conjugates, and even diubiquitin dimers can be prepared through this approach. The low excess of reagent needed, mild reaction conditions used, short reaction times, and stability of the S-C(alkyne) bonds at physiological conditions make this approach an interesting addition to the toolbox of classical, site-selective cysteine-conjugation methods.

Description

Keywords

Alkynes, Animals, Chemistry Techniques, Synthetic, Cysteine, Humans, Indicators and Reagents, Mesylates, Models, Molecular, Proteins, Sulfhydryl Compounds, Thiophenes

Journal Title

Bioconjug Chem

Conference Name

Journal ISSN

1043-1802
1520-4812

Volume Title

32

Publisher

American Chemical Society (ACS)

Rights

All rights reserved
Sponsorship
Royal Society (URF\R\180019)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (836698)
European Research Council (337969)