Related Experiment Video
Updated: Oct 28, 2025

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry
Published on: July 20, 2016
Rapid and robust cysteine bioconjugation with vinylheteroarenes
Hikaru Seki1, Stephen J Walsh1,2, Jonathan D Bargh1
1Department of Chemistry, University of Cambridge Lensfield Road Cambridge CB2 1EW UK spring@ch.cam.ac.uk.
Abstract:
Methods for residue-selective and stable modification of canonical amino acids enable the installation of distinct functionality which can aid in the interrogation of biological processes or the generation of new therapeutic modalities. Herein, we report an extensive investigation of reactivity and stability profiles for a series of vinylheteroarene motifs. Studies on small molecule and protein substrates identified an optimum vinylheteroarene scaffold for selective cysteine modification. Utilisation of this lead linker to modify a number of protein substrates with various functionalities, including the synthesis of a homogeneous, stable and biologically active antibody-drug conjugate (ADC) was then achieved. The reagent was also efficient in labelling proteome-wide cysteines in cell lysates. The efficiency and selectivity of these reagents as well as the stability of the products makes them suitable for the generation of biotherapeutics or studies in chemical biology.
Related Concept Videos
Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
Phase II Reactions: Sulfation and Conjugation with α-Amino Acids
Carboxylic Acids to Methylesters: Alkylation using Diazomethane
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Conjugate Addition to α,β-Unsaturated Carbonyl Compounds
Esters to β-Ketoesters: Claisen Condensation Mechanism

