Version 1
: Received: 2 May 2021 / Approved: 5 May 2021 / Online: 5 May 2021 (11:50:39 CEST)
Version 2
: Received: 18 October 2021 / Approved: 19 October 2021 / Online: 19 October 2021 (10:28:15 CEST)
How to cite:
Long, M.; Ly, P.; Aye, Y. A Primer on Harnessing Non-enzymatic Posttranslational Modifications for Drug Design. Preprints2021, 2021050036. https://doi.org/10.20944/preprints202105.0036.v1
Long, M.; Ly, P.; Aye, Y. A Primer on Harnessing Non-enzymatic Posttranslational Modifications for Drug Design. Preprints 2021, 2021050036. https://doi.org/10.20944/preprints202105.0036.v1
Long, M.; Ly, P.; Aye, Y. A Primer on Harnessing Non-enzymatic Posttranslational Modifications for Drug Design. Preprints2021, 2021050036. https://doi.org/10.20944/preprints202105.0036.v1
APA Style
Long, M., Ly, P., & Aye, Y. (2021). A Primer on Harnessing Non-enzymatic Posttranslational Modifications for Drug Design. Preprints. https://doi.org/10.20944/preprints202105.0036.v1
Chicago/Turabian Style
Long, M., Phillippe Ly and Yimon Aye. 2021 "A Primer on Harnessing Non-enzymatic Posttranslational Modifications for Drug Design" Preprints. https://doi.org/10.20944/preprints202105.0036.v1
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.
Keywords
Electrophile; Drug Design; Covalent Drug; Chemical Biology
Subject
Chemistry and Materials Science, Analytical Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
