INTRAMOLECULAR FOLDING OF PYRIMIDINE OLIGODEOXYNUCLEOTIDES INTO AN I-DNA MOTIF

At slightly acidic or even neutral pH, oligodeoxynucleotides which inc lude a stretch of cytidines form a tetrameric structure in which two p arallel-stranded duplexes have their hemiprotonated C.C+ base pairs fa ce to face and fully intercalated, in a so-called i-motif, first obser ved for d-TCCCCC. Cytosine-rich pyrimidine oligodeoxynucleotides, 14-3 0 bases long, can form an intramolecular ''i-motif', in a manner simil ar to that observed in strands of telomeric repeat sequences (Leroy et al. Nucleic Acids Res. 1994, 22, 1600-1606). This intramolecular i-mo tif can accommodate as few as eight cytosines (four intercalated C.Cbase pairs), Evidence for intramolecular pairing was provided by therm al denaturation, nondenaturing gel electrophoresis, and gel filtration experiments and was characterized by specific NMR cross-peaks, The st ability of a C.C+ base pair is very high at pH 5 and still detectable at neutral pH. Formation of the i-motif, whether intramolecular or int ermolecular, should be taken into account as a competing structure in the design of triplex-forming oligodeoxynucleotides.