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

AVIÑÓ, ANNA; DELLAFIORE, MARÍA; GARGALLO, RAIMUNDO; GONZÁLEZ, CARLOS; IRIBARREN, ADOLFO M.; MONTSERRAT, JAVIER; ERITJA, RAMON

CHEMBIOCHEM

WILEY-V C H VERLAG GMBH

Año: 2017

1439-4227

 G-quadruplex  and i-motif are tetraplex structures present in telomeres  and  promoter regions  of  oncogenes. The  possibility  of producing nanodevices with pH-sensitive functions has triggered the interest  for  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  related  to  vertebrate  telomere  was investigated by means of spectroscopic methods (UV, CD and NMR). The  replacement  of  selected  positions  of  the  C-core  by  the appropriate  C-modified  residues  induces  the  formation  of  stable intercalated  tetraplexes  at  pHs  near  neutrality.  The  study demonstrates  the  possibility  of  enhancing  the  stability  of  i-motif  by chemical modifications