title: Structural evaluation of tandem hairpin pyrrole-imidazole polyamides recognizing human telomeres.
abstract: A polyamide containing N-methylpyrrole (Py) and N-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(CH2)3N(CH3)-(CH2)3NH-[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(C2H4O)2(C2H4)CO-] with tetramethylrhodamine as the fluorescent dye.
authors.affiliation: HiPep Laboratories, Nakatsukasa-cho 486-46, Kamigyo-ku Kyoto, 602-8158, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hirata
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Nokihara
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamoto
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.forename: Asuka
authors.initials: A
authors.lastname: Sasaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Ide
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Maeshima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kasama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D004247:DNA / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D009757:Nylons / Q000737:chemistry*; D011485:Protein Binding; D011758:Pyrroles / Q000737:chemistry*; D012235:Rhodamines / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D020349:Surface Plasmon Resonance; D053719:Tandem Mass Spectrometry; D016615:Telomere / Q000737:chemistry / Q000648:ultrastructure*; D013696:Temperature; D013816:Thermodynamics; D014966:Xanthenes / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; D012235:Rhodamines; D014966:Xanthenes; C005358:tetramethylrhodamine; C034657:Texas red; D004247:DNA