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.

Unnatural bases for recognition of noncoding nucleic acid interfaces

“…A, N7‐linked guanine ( 7 G) and guanine mimic N7‐pyrazole (P1); [ 13,91 ] B, TRIPside bases that cross the major groove while minimizine third strand displacement. [ 126 ] Arrows indicate 5′‐3′ directionality of sugar‐phosphate backbone…”

Towards the Sequence‐Selective Recognition of Double‐Stranded DNA Containing Pyrimidine‐Purine Interruptions by Triplex‐Forming Oligonucleotides

“…However, when a long (30-mer), random and non-alternating α,β-oligodeoxycytidylate was used as a TFO, α-and β-protonated C (C + H) was able to bind to TA and AT base pairs, respectively. [85][86][87][88] The nucleobases in the TRIPsides preferentially adopted anti conformations due to steric hindrance between the nucleobases and the sugar moieties. [82] Leumann's group, on the other hand, examined hypoxanthin-7-yl, 2-aminopurin-7-yl or 2-aminopurin-9-yl nucleobases in a similar approach.…”

“…[81] α-T was also shown to recognize single and quintuple TA base pairs in the chimeric α,β-TFOs, although the presence of three dispersed TA base pairs prevented triplex formation, probably due to the lost stacking interactions between the base triplets. [85] Triplex formation of oligoTRIPs with any dsDNA sequence will be very interesting in terms of their practical uses. [83,84] When 15-mer TFOs containing 2-aminopurin-7-yl nucleobases (α-7AP or β-7AP, Figure 33) with α-or β-configuration at a single position were used, α-7AP and β-7AP were able to bind selectively to TA and AT base pairs, respectively.…”

Direct detection of double-stranded DNA: molecular methods and applications for DNA diagnostics

“…For example, artificial base analogs can extend recognition to all possible base pairs. 35 Chemical compounds such as BQQ can act as triplex stabilizing agents. 36 Triplex formation involving any sequence of bases was suggested to occur at physiological pH in the presence of YOYO-1, an oxazole yellow homodimer the fluorescent intensity of which increases over 1 000-fold in the presence of dsDNA and 100 000-fold in the presence of triplex DNA.…”