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Updated: Jul 12, 2026

Synthesis of 1,2-Azaborines and the Preparation of Their Protein Complexes with T4 Lysozyme Mutants
Published on: March 25, 2017
Benzoxaboroles Are Structurally Unique Binders of Eukaryotic Translation Initiation Factor 4E
Joshua B Combs1, D Matthew Peacock1, Gregory B Craven1
1Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California 94158, United States.
Abstract:
Benzoxaboroles offer unusual reactivity and protein recognition for the development of small molecule drugs. Despite this potential, they are uncommon in drug discovery or in fragment screening libraries. We synthesized a series of structurally related benzoxaboroles containing a diazirine/alkyne tag to enable in-cell photoaffinity labeling experiments. A subset of this library was found to have high selectivity for eukaryotic translation initiation factor 4E (eIF4E). The benzoxaborole-eIF4E interaction was found to be stereoselective in nature and competitive with the 7-methylguanosine cap of mRNA. Site of labeling experiments revealed that the benzoxaborole fragment interacts with the cap binding pocket of eIF4E. In silico modeling of the modified protein suggests that H-bonding interactions between the main chain of Trp102 and the side chain of Asn155 to the amide carbonyl and anionic boronate of the benzoxaborole, respectively, drive affinity for this challenging to drug pocket.
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