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Scientific article
English

Screening for covalent inhibitors using DNA-display of small molecule libraries functionalized with cysteine reactive moieties

Published inMedChemComm, vol. 7, no. 7, p. 1340-1351
Publication date2016
Abstract

DNA-encoded chemical libraries are increasingly used to identify leads for drug discovery or chemical biology. Despite the resurging interest in covalent inhibitors, libraries are typically designed with synthon filtered out for reactive functionalities that can engage a target through covalent interactions. Herein, we report the synthesis of two libraries containing Michael acceptors to identify cysteine reactive ligands. We developed a simple procedure to discriminate between covalent and high affinity non-covalent inhibitors using DNA display of the library in a microarray format. The methodology was validated with known covalent and high affinity non-covalent kinase inhibitors. Screening of the library revealed novel covalent inhibitors for MEK2 and ERBB2.

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Citation (ISO format)
ZAMBALDO, Claudio et al. Screening for covalent inhibitors using DNA-display of small molecule libraries functionalized with cysteine reactive moieties. In: MedChemComm, 2016, vol. 7, n° 7, p. 1340–1351. doi: 10.1039/C6MD00242K
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ISSN of the journal2040-2503
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Technical informations

Creation07/13/2016 10:25:00 AM
First validation07/13/2016 10:25:00 AM
Update time03/15/2023 12:32:53 AM
Status update03/15/2023 12:32:52 AM
Last indexation01/16/2024 9:17:38 PM
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