Molecular recognition via triplex formation of mixed purine/pyrimidine DNA sequences using oligoTRIPs.

ABSTRACT

Stable DNA triple-helical structures are normally restricted to homopurine sequences. We have described a system of four heterocyclic bases (TRIPsides) that, when incorporated into oligomers (oligoTRIPs), can recognize and bind in the major groove to any native sequence of DNA [Li et al., J. Am. Chem. Soc. 2003, 125, 2084]. To date, we have reported on triplex-forming oligomers composed of two of these TRIPsides, i.e., antiTA and antiGC, and their ability to form intramolecular triplexes at mixed purine/pyrimidine sequences. In the present study, we describe the synthesis and characterization of the antiCG TRIPside and its use in conjunction with antiTA and antiGC to form sequence-specific intra- and/or intermolecular triplex structures at mixed purine/pyrimidine sequences that require as many as four major groove crossovers.