Issue 11, 2021

A primer on harnessing non-enzymatic post-translational modifications for drug design

Abstract

Of the manifold concepts in drug discovery and design, covalent drugs have re-emerged as one of the most promising over the past 20-or so years. All such drugs harness the ability of a covalent bond to drive an interaction between a target biomolecule, typically a protein, and a small molecule. Formation of a covalent bond necessarily prolongs target engagement, opening avenues to targeting shallower binding sites, protein complexes, and other difficult to drug manifolds, amongst other virtues. This opinion piece discusses frameworks around which to develop covalent drugs. Our argument, based on results from our research program on natural electrophile signaling, is that targeting specific residues innately involved in native signaling programs are ideally poised to be targeted by covalent drugs. We outline ways to identify electrophile-sensing residues, and discuss how studying ramifications of innate signaling by endogenous molecules can provide a means to predict drug mechanism and function and assess on- versus off-target behaviors.

Graphical abstract: A primer on harnessing non-enzymatic post-translational modifications for drug design

Article information

Article type
Opinion
Submitted
05 Mai 2021
Accepted
08 Okt 2021
First published
26 Okt 2021

RSC Med. Chem., 2021,12, 1797-1807

A primer on harnessing non-enzymatic post-translational modifications for drug design

M. J. C. Long, P. Ly and Y. Aye, RSC Med. Chem., 2021, 12, 1797 DOI: 10.1039/D1MD00157D

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