Overview of the assays to probe O-linked β-N-acetylglucosamine transferase binding and activity

Balsollier, Cyril (author), Pieters, Roland J. (author), Anderluh, Marko (author)

O-GlcNAcylation is a posttranslational modification that occurs at serine and threonine residues of protein substrates by the addition of O-linked β-D-N-acetylglucosamine (GlcNAc) moiety. Two enzymes are involved in this modification: O-GlcNac transferase (OGT), which attaches the GlcNAc residue to the protein substrate, and O-GlcNAcase (OGA), which removes it. This biological balance is important for many biological processes, such as protein expression, cell apoptosis, and regulation of enzyme activity. The extent of this modification has sparked interest in the medical community to explore OGA and OGT as therapeutic targets, particularly in degenerative diseases. While some OGA inhibitors are already in phase 1 clinical trials for the treatment of Alzheimer’s disease, OGT inhibitors still have a long way to go. Due to complex expression and instability, the discovery of potent OGT inhibitors is challenging. Over the years, the field has grappled with this problem, and scientists have developed a number of techniques and assays. In this review, we aim to highlight assays and techniques for OGT inhibitor discovery, evaluate their strength for the field, and give us direction for future bioassay methods.

• Language: English
• Keywords: OGT, GlcNAcylation, O-GlcNAc transferase, bioassay, OGT inhibitor
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 20 str.
• Numbering: Vol. 26, iss. 4, art. 1037
• PID: 20.500.12556/RUL-135020
• UDC: 615.4:54:616.894
• ISSN on article: 1420-3049
• DOI: 10.3390/molecules26041037
• COBISS.SI-ID: 51829507
• Publication date in RUL: 17.02.2022

Record is a part of a journal

• Title: Molecules
• Shortened title: Molecules
• Publisher: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 16.02.2021

Secondary language

• Language: Slovenian
• Keywords: farmacevtska kemija, Alzheimerjeva bolezen

Projects

• Funder: EC - European Commission
• Funding programme: H2020
• Project number: 765581
• Name: Multidisciplinary European Joint Doctorate in the Design and Development of Glyco Drugs
• Acronym: PhD4GlycoDrug