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Rapid and robust cysteine bioconjugation with vinylheteroarenes
- Source :
- Chemical Science
- Publication Year :
- 2021
- Publisher :
- Royal Society of Chemistry (RSC), 2021.
-
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.<br />Vinylheteroarene linkers can chemoselectively modify cysteine residues in proteins and antibodies. These linkers give stable bioconjugates, and were used to synthesise efficacious antibody-drug conjugates.
- Subjects :
- chemistry.chemical_classification
Bioconjugation
34 Chemical Sciences
Chemical biology
3405 Organic Chemistry
General Chemistry
Combinatorial chemistry
Small molecule
Amino acid
Chemistry
chemistry
Reagent
Generic health relevance
3404 Medicinal and Biomolecular Chemistry
Linker
Conjugate
Cysteine
Biotechnology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Chemical Science
- Accession number :
- edsair.doi.dedup.....32ee870e417d5cb77a7bfd9398826717
- Full Text :
- https://doi.org/10.17863/cam.74428