Triple helix forming TRIPside molecules that target mixed purine/pyrimidine DNA sequences.

A new strategy to form stable and sequence-specific triple helical DNA structures at mixed purine/pyrimidine sequences using a combination of four C-glycosides (TRIPsides) has been described [Li et al. (2003) J. Am. Chem. Soc. 125, 2084]. The partial realization of the approach is demonstrated by incorporating two of the four TRIPsides into oligomers that can potentially fold into intramolecular triplexes that contain one or two major groove crossovers of the purine Hoogsteen H-bond information. Using temperature-dependent electronic and fluorescence spectroscopy and differential scanning calorimetry, it is demonstrated that stable triplexes form at physiological conditions at non-homopurine targets. In addition, triplexes using the TRIPsides form in a highly sequence specific manner.