Stabilization of Telomeric I-Motif Structures by (2′S)-2′-Deoxy-2′-C-Methylcytidine Residues

Abstract

G-quadruplexes and i-motifs are tetraplex structures present in telomeres and the promoter regions of oncogenes. The possibility of producing nanodevices with pH-sensitive functions has triggered interest in modified oligonucleotides with improved structural properties. We synthesized C-rich oligonucleotides carrying conformationally restricted (2′S)-2′-deoxy-2′-C-methyl-cytidine units. The effect of this modified nucleoside on the stability of intramolecular i-motifs from the vertebrate telomere was investigated by UV, CD, and NMR spectroscopy. The replacement of selected positions of the C-core with C-modified residues induced the formation of stable intercalated tetraplexes at near-neutral pH. This study demonstrates the possibility of enhancing the stability of the i-motif by chemical modification. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim