Cited by 331Organoboron and organosilicon chemistryClick Chemistry and ApplicationsBoron Compounds in Chemistry

The versatility of boron in biological target engagement

Diaz, Diego B., Yudin, Andrei K.·2017·Nature Chemistry

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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Crossref · 10.1038/nchem.2814

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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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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
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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