Efficient inhibition of human AP endonuclease 1 (APE1) via substrate masking by abasic site-binding macrocyclic ligands

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.