Issue 16, 2022

Methods to characterize and discover molecular degraders in cells

Abstract

Cells use many post-translational modifications (PTMs) to tailor proteins and transduce cellular signals. Recent years have witnessed the rapid growth of small molecule and enzymatic strategies to purposely manipulate one particular PTM, ubiquitination, on desired target proteins in cells. These approaches typically act by induced proximity between an E3 ligase and a target protein resulting in ubiquitination and degradation of the substrate in cells. In this review, we cover recent approaches to study molecular degraders and discover their induced substrates in vitro and in live cells. Methods that have been adapted and applied to the development of molecular degraders are described, including global proteomics, affinity-purification, chemical proteomics and enzymatic strategies. Extension of these strategies to edit additional PTMs in cells is also discussed. This review is intended to assist researchers who are interested in editing PTMs with new modalities to select suitable method(s) and guide their studies.

Graphical abstract: Methods to characterize and discover molecular degraders in cells

Article information

Article type
Review Article
Submitted
02 apr 2022
First published
28 jul 2022

Chem. Soc. Rev., 2022,51, 7115-7137

Methods to characterize and discover molecular degraders in cells

Z. Lin and C. M. Woo, Chem. Soc. Rev., 2022, 51, 7115 DOI: 10.1039/D2CS00261B

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements