Stabilization of the i-motif structure by the intra-strand cross-link formation

作者：Kikuta Kenji; Piao Haishun; Brazier John; Taniguchi Yosuke; Onizuka Kazumitsu; Nagatsugi Fumi; Sasaki Shigeki^*

来源：Bioorganic & Medicinal Chemistry Letters, 2015, 25(16): 3307-3310.

DOI：10.1016/j.bmcl.2015.05.064

• i-Motif
• Intrastrand cross-link
• Thermal stability
• Entropy
• Enthalpy

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.

• 出版日期2015-8-15