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A Small Molecule Affecting the Replication of Trinucleotide Repeat d(GAA) n
Author(s) -
He Hanping,
Hagihara Masaki,
Nakatani Kazuhiko
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200901088
Subject(s) - circular dichroism , taq polymerase , chemistry , surface plasmon resonance , polymerase , dna polymerase , dna , microbiology and biotechnology , dimer , crystallography , thermus aquaticus , biology , biochemistry , materials science , nanotechnology , organic chemistry , nanoparticle
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 GG 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 α.