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.
MeSH terms
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Animals
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Aurintricarboxylic Acid / pharmacology
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Cattle
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DNA / chemistry
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DNA-(Apurinic or Apyrimidinic Site) Lyase / antagonists & inhibitors*
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DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology*
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Ethidium / pharmacology
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Humans
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Indoles / pharmacology
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Intercalating Agents / chemistry*
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Intercalating Agents / pharmacology*
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Kinetics
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Ligands*
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Macrocyclic Compounds / chemistry*
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Macrocyclic Compounds / pharmacology*
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Naphthalenes / chemistry*
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Naphthalenes / pharmacology*
Substances
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7-nitro-1H-indole-2-carboxylic acid
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Enzyme Inhibitors
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Indoles
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Intercalating Agents
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Ligands
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Macrocyclic Compounds
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Naphthalenes
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Aurintricarboxylic Acid
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DNA
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calf thymus DNA
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APEX1 protein, human
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DNA-(Apurinic or Apyrimidinic Site) Lyase
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Ethidium