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Updated: Apr 3, 2026

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1
Published on: April 16, 2021
Efficient inhibition of human AP endonuclease 1 (APE1) via substrate masking by abasic site-binding macrocyclic
Naoko Kotera1, Florent Poyer, Anton Granzhan
1CNRS UMR9187/INSERM U1196 "Chemistry, Modelling and Imaging for Biology", Centre de Recherche, Institut Curie, 91405 Orsay, France. anton.granzhan@curie.fr.
Abstract:
Bis-naphthalene macrocycles, which bind with high affinity and selectivity to abasic sites in DNA, efficiently inhibit their cleavage by APE1 (IC50 = 55-60 nM in the kinetic assay with a model THF substrate). These results demonstrate that substrate masking by non-covalent abasic-site ligands is an efficient strategy for inhibition of APE1.
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