Covalent chemical probes – chemical probes that form a covalent bond with their target biomacromolecule(s) represent powerful tools that can be used for biology discovery, target validation (or off-target identification), and as starting points for drug discovery programmes.
Drugs with a covalent mode of action have been known and used for over a century, although historically, pursuit of such bioactive compounds has been avoided due to concerns over lack of selectivity. Over the last three decades, however, the use of ligands bearing reactive handles has seen increased interest spawning efforts to rationally design covalent drugs and new approaches to study protein function such as activity-based protein-profiling. Where covalent bioactive ligands are concerned, increased selectivity and duration of action represent advantages. In the context of new methods to study biology, chemical methods uniquely offer the ability to develop new reactive warheads, optimize bioorthogonal chemistries, and label a protein-of-interest with a (multi)functional group of choice, including natural or non-natural functionalities harbouring a recognition, reporting or affinity handle. Collectively, this offers new opportunities to modulate, track and isolate proteins of interest in/from the complex cellular milieu. In turn, this has created demand for new regioselective chemistries and analytical methods to assess biomacromolecule labelling in the complex environment of the cell.
This Guest Edited Collection aims to bring together research across the broad remit of covalent biomacromolecule labelling chemistry. We welcome both experimental and theoretical studies, with topics of interest including but not limited to:
- New chemistry for protein modification
- Photoaffinity labelling
- Protein target identification
- Chemical proteomics or chemoproteomics
- Activity based protein profiling
- Proximity-based labelling
- Bioorthogonal chemistry
- Covalent inhibitors
- Covalent degraders
- Understanding post-translational modifications using chemical approaches
In addition to primary research Articles, we also welcome Perspectives, Reviews, and Comments. All submissions will be subject to the same review process and editorial standards as regular Communications Chemistry Articles.
The team of Editors working on this Collection is:
Guest Editor Keriann Marie Backus, UCLA, USA
See here for full details: https://www.nature.com/collections/iecefbbafa
Image credit: Andy Wilson