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Rapid and robust cysteine bioconjugation with vinylheteroarenes.

Published version
Peer-reviewed

Type

Article

Change log

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.

Description

Keywords

3404 Medicinal and Biomolecular Chemistry, 3405 Organic Chemistry, 34 Chemical Sciences, Biotechnology, Immunization, Generic health relevance

Journal Title

Chem Sci

Conference Name

Journal ISSN

2041-6520
2041-6539

Volume Title

12

Publisher

Royal Society of Chemistry (RSC)
Sponsorship
Engineering and Physical Sciences Research Council (EP/P020291/1)