title: Stabilization of the i-motif structure by the intra-strand cross-link formation.
abstract: The i-motif structures are formed by oligonucleotides containing cytosine tracts under acidic conditions. The folding of the i-motif under physiological conditions is of great interest because of its biological role. In this study, we investigated the effect of the intra-strand cross-link on the stability of the i-motif structure. The 4-vinyl-substituted analog of thymidine (T-vinyl) was incorporated into the 5'-end of the human telomere complementary strand, which formed the intra-strand cross-link with the internal adenine. The intra-strand cross-linked i-motif displayed CD spectra similar to that of the natural i-motif at acidic pH, which was transformed into a random coil with the increasing pH. The pH midpoint for the transition from the i-motif to random coil increased from pH 6.1 for the natural one to pH 6.8 for the cross-linked one. The thermodynamic parameters were obtained by measuring the thermal melting behaviors by CD and UV, and it was determined that the intra-strand cross-linked i-motif is stabilized due to a favorable entropy effect. Thus, this study has clearly indicated the validity of the intra-strand cross-linking for stabilization of the i-motif structure.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kikuta
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Haishun
authors.initials: H
authors.lastname: Piao
authors.affiliation: School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, UK.
authors.forename: John
authors.initials: J
authors.lastname: Brazier
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Taniguchi
authors.affiliation: Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Onizuka
authors.affiliation: Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.
authors.forename: Fumi
authors.initials: F
authors.lastname: Nagatsugi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: sasaki@phar.kyushu-u.ac.jp.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sasaki
mesh_terms: D020816:Amino Acid Motifs / Q000502:physiology; D002942:Circular Dichroism; D003596:Cytosine / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D016615:Telomere / Q000737:chemistry
chemical_list: D009841:Oligonucleotides; D003596:Cytosine
keywords: Enthalpy; Entropy; Intrastrand cross-link; Thermal stability; i-Motif