The versatility of boron in biological target engagement
Abstract
Boron-containing molecules have been extensively used for the purposes of chemical sensing, biological probe development and drug discovery. Due to boron's empty p orbital, it can coordinate to heteroatoms such as oxygen and nitrogen. This reversible covalent mode of interaction has led to the use of boron as bait for nucleophilic residues in disease-associated proteins, culminating in the approval of new therapeutics that work by covalent mechanisms. Our analysis of a wide range of covalent inhibitors with electrophilic groups suggests that boron is a unique electrophile in its chameleonic ability to engage protein targets. Here we review boron's interactions with a range of protein side-chain residues and reveal that boron's properties are nuanced and arise from its uncommon coordination preferences. These mechanistic and structural insights should serve as a guide for the development of selective boron-based bioactive molecules.
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Several additional boron-containing drugs inhibit serine hydrolases beyond the proteasome by forming covalent adducts between catalytic serine residues and boron.
“Several additional boron-containing drugs inhibit serine hydrolases beyond the proteasome through formation of covalent adducts between catalytic serine residues and boron133,134.”
From Advances in covalent drug discovery (2022) · cites this paper as [133]
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Advances in covalent drug discovery
Boike, L., Henning, N. J., & Nomura, D. K. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00542-z · Cited by 823 · see citing works
- Authors
- Diaz, D. B., & Yudin, A. K.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Yudin, Andrei K.
- Venue
- Nature Chemistry
- Published
- 2017-07-25
- Volume
- 9
- Issue
- 8
- Pages
- 731-742
- ISSN
- 1755-4330 (ISSN-L)
- 1755-4349
- OpenAlex
- W2736830325
- Cited by
- 331
- References
- 70
- Citations by year
- 2026: 27 · 2025: 45 · 2024: 31 · 2023: 36 · 2022: 44 · 2021: 46 · 2020: 26 · 2019: 34 · 2018: 35 · 2017: 7
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Organoboron and organosilicon chemistry
- Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Boron Compounds in Chemistry
- Keywords
- boron, covalent inhibitors, coordination modes, protein-ligand interactions
- MeSH terms
- Boron Compounds, Enzyme Inhibitors, Enzymes, Humans, Proteins, Molecular Probes, Molecular Structure, Catalytic Domain
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