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Issue 17, 2015
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Facile synthesis of borofragments and their evaluation in activity-based protein profiling

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Abstract

The discovery of enzyme inhibitors relies on synthetic methods that enable rapid and modular construction of small molecules. Heterocyclic fragments designed to maximize enthalpic interactions with their protein targets represent a particularly desirable class of molecules. Here we describe a reagent that enables straightforward construction of “borofragments”, in which a heterocycle is separated from the boron center by two or three rotatable bonds. The stability of these molecules depends on the MIDA group which likely acts as a slow-release element under biological conditions. Borofragments can be used to discover inhibitors of enzymes that use catalytic oxygen nucleophiles. We have employed this method to identify inhibitors of ABHD10 and the predicted carboxypeptidase CPVL. This technique should be applicable to other classes of targets.

Graphical abstract: Facile synthesis of borofragments and their evaluation in activity-based protein profiling

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Publication details

The article was received on 14 Nov 2014, accepted on 12 Jan 2015 and first published on 14 Jan 2015


Article type: Communication
DOI: 10.1039/C4CC09107H
Chem. Commun., 2015,51, 3608-3611

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    Facile synthesis of borofragments and their evaluation in activity-based protein profiling

    S. Adachi, A. B. Cognetta, M. J. Niphakis, Z. He, A. Zajdlik, J. D. St. Denis, C. C. G. Scully, B. F. Cravatt and A. K. Yudin, Chem. Commun., 2015, 51, 3608
    DOI: 10.1039/C4CC09107H

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