The unexplored potential of quinone methides in chemical biology
File(s)
Accepted version
Author(s)
Di Antonio, Marco
Minard, Aisling
Liano, Denise
Wang, Xiaofan
Type
Journal Article
Abstract
Quinone methides (QMs) are transient reactive species that can be efficiently generated from stable precursors under a variety of biocompatible conditions. Due to their electrophilic nature, QMs have been widely explored as cross-linking agents of DNA and proteins under physiological conditions. However, QMs also have a diene character and can irreversibly react via Diels-Alder reaction with electron-rich dienophiles. This particular reactivity has been recently exploited to label biomolecules with fluorophores in living cells.
QMs are characterised by two unique properties that make them ideal candidates for chemical biology applications: i) they can be efficiently generated in situ from very stable precursors by means of bio-orthogonal protocols ii) they are reversible cross-linking agents, making them suitable for “catch and release” target-enrichment experiments. Nevertheless, there are only few examples reported to date that truly take advantage of QMs unique chemistry in the context of chemical-biology assay development. In this review, we will examine the most relevant examples that illustrate the benefit of using QMs for chemical biology purposes and we will anticipate novel approaches to further their applications in biologically relevant contexts.
QMs are characterised by two unique properties that make them ideal candidates for chemical biology applications: i) they can be efficiently generated in situ from very stable precursors by means of bio-orthogonal protocols ii) they are reversible cross-linking agents, making them suitable for “catch and release” target-enrichment experiments. Nevertheless, there are only few examples reported to date that truly take advantage of QMs unique chemistry in the context of chemical-biology assay development. In this review, we will examine the most relevant examples that illustrate the benefit of using QMs for chemical biology purposes and we will anticipate novel approaches to further their applications in biologically relevant contexts.
Date Issued
2019-06-15
Date Acceptance
2019-04-01
Citation
Bioorganic and Medicinal Chemistry, 2019, 27 (12), pp.2298-2305
ISSN
0968-0896
Publisher
Elsevier
Start Page
2298
End Page
2305
Journal / Book Title
Bioorganic and Medicinal Chemistry
Volume
27
Issue
12
Copyright Statement
© 2019 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
Biotechnology and Biological Sciences Research Council (BBSRC)
Grant Number
BB/R011605/1
Subjects
Bioorthogonal ligations
Chemical-biology
Cross-linking
Live-cell imaging
Photo-click chemistry
Quinone methides
0304 Medicinal and Biomolecular Chemistry
1115 Pharmacology and Pharmaceutical Sciences
0305 Organic Chemistry
Medicinal & Biomolecular Chemistry
Publication Status
Published
Date Publish Online
2019-04-02