Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 15, Issue 40, Pages 10641-10648Publisher
WILEY-BLACKWELL
DOI: 10.1002/chem.200901088
Keywords
DNA recognition; ligand design; nucleotides; polymerases; small molecules
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Funding
- Japan Society for the Promotion of Science (JSPS) [18105006, 06061]
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A newly designed ligand, methylcarbamoylnaphthyridine dimer (MCND), was synthesized and characterized. Ligand binding to d(GAA)(10) was investigated by UV thermal denaturation, circular dichroism spectroscopy, surface plasmon resonance, and cold-spray-ionization time-of-flight mass spectrometry. The results indicated that MCND bound to the d(GAA)(n) repeat to form a stable hairpin structure with a major binding stoichiometry of 3:1. The most likely binding site was identified as the G-G mismatch in the AGA/AGA triad. The polymerase stop assay showed that MCND binding to the d(GAA)(n) repeat effectively interfered with the extension of the primer at the first two GAA sites on the template with both prokaryotic Taq DNA polymerase and human DNA polymerase alpha.
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