The binding of a dimeric form of the 2-amino-1,8-naphthyridine derivative (naphthyridine dimer)to a human telomeric sequence, TTAGGG, was investigated by UV melting, CD spectra, and CSI-MSmeasurements. Both the 9-mer d(TTAGGGTTA) and the 15-mer d(TTAGGGTTAGGGTTA) showedapparent melting temperatures (
Tm) of 45.6 and 63.6
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C, respectively, in the presence of naphthyridinedimer (30
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M) in sodium cacodylate buffer (50 mM, pH 7.0) containing 100 mM NaCl. The CD spectra at235 and 255 nm of the 9-mer increased in intensity accompanied with strong induced CDs at 285 and 340nm upon complex formation with naphthyridine dimer. UV titration of the binding of naphthyridine dimer tothe 9-mer at 320 nm showed a hypochromism of the spectra. A Scatchard plot of the data showed thepresence of multiple binding sites with different association constants. Cold spray ionization massspectrometry of the complex between naphthyridine dimer and the 9-mer clearly showed that one to threemolecules of the ligand bound to the dimer duplex of the 9-mer. Telomeric repeat elongation assay showedthat the binding of naphthyridine dimer to the telomeric sequence inhibits the elongation of the sequenceby telomerase.