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

Kikuta, K., Piao, H., Brazier, J. ORCID: https://orcid.org/0000-0002-4952-584X, Taniguchi, Y., Onizuka, K., Nagatsugi, F. and Sasaki, S. (2015) Stabilization of the i-motif structure by the intra-strand cross-link formation. Bioorganic & Medicinal Chemistry Letters, 25 (16). pp. 3307-3310. ISSN 0960-894X doi: 10.1016/j.bmcl.2015.05.064

Abstract/Summary

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.