Structural
Evaluation of Tandem Hairpin Pyrrole–Imidazole
Polyamides Recognizing Human Telomeres
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Abstract
A polyamide containing <i>N</i>-methylpyrrole (Py) and <i>N</i>-methylimidazole
(Im), designated PIPA, binds with high
affinity and specificity to specific nucleotide sequences in the minor
groove of double-helical DNA. Based on a recent report of the synthesis
of PIPA for telomere visualization, the present paper focused on the
size of the connecting part (hinge region) of two PIPA segments of
the tandem hairpin PIPA, Dab(Im-Im-Py)-Py-Py-Py-Im-[Hinge]-Dab(Im-Im-Py)-Py-Py-Py-Im-βAla-NH(CH<sub>2</sub>)<sub>3</sub>N(CH<sub>3</sub>)-(CH<sub>2</sub>)<sub>3</sub>NH-[Dye]. The present paper also describes the characterization of
binding by measuring the thermal melting temperature and surface plasmon
resonance and by specific staining of telomeres (TTAGGG)n in human
cells. Microheterogeneity was also investigated by high-resolution
mass spectrometry. We found that the optimal compound as the hinge
segment for telomere staining was [-NH(C<sub>2</sub>H<sub>4</sub>O)<sub>2</sub>(C<sub>2</sub>H<sub>4</sub>)CO-] with tetramethylrhodamine
as the fluorescent dye
