University of Oulu

Glumoff, T., Sowa, S. T., & Lehtiö, L. (2022). Assay technologies facilitating drug discovery for ADP-ribosyl writers, readers and erasers. BioEssays, 44, e2100240. https://doi.org/10.1002/bies.202100240

Assay technologies facilitating drug discovery for ADP-ribosyl writers, readers and erasers

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Author: Glumoff, Tuomo1; Sowa, Sven T.1; Lehtiö, Lari1
Organizations: 1Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2021122162418
Language: English
Published: John Wiley & Sons, 2021
Publish Date: 2022-11-23
Description:

Abstract

ADP-ribosylation is a post-translational modification catalyzed by writer enzymes — ADP-ribosyltransferases. The modification is part of many signaling events, can modulate the function and stability of target proteins, and often results in the recruitment of reader proteins that bind to the ADP-ribosyl groups. Erasers are integral actors in these signaling events and reverse the modification. ADP-ribosylation can be targeted with therapeutics and many inhibitors against writers exist, with some being in clinical use. Inhibitors against readers and erasers are sparser and development of these has gained momentum only in recent years. Drug discovery has been hampered by the lack of specific tools, however many significant advances in the methods have recently been reported. We discuss assays used in the field with a focus on methods allowing efficient identification of small molecule inhibitors and profiling against enzyme families. While human proteins are focused, the methods can be also applied to bacterial toxins and virus encoded erasers that can be targeted to treat infectious diseases in the future.

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Series: BioEssays
ISSN: 0265-9247
ISSN-E: 1521-1878
ISSN-L: 0265-9247
Volume: 44
Issue: 1
Article number: 2100240
DOI: 10.1002/bies.202100240
OADOI: https://oadoi.org/10.1002/bies.202100240
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Subjects:
Funding: The work was supported by Jane and Aatos Erkko foundation.
Copyright information: © 2021 Wiley Periodicals LLC. This is the peer reviewed version of the following article: Glumoff, T., Sowa, S. T., & Lehtiö, L. (2022). Assay technologies facilitating drug discovery for ADP-ribosyl writers, readers and erasers. BioEssays, 44, e2100240, which has been published in final form at https://doi.org/10.1002/bies.202100240. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.