Synthesis of a neomycin-Hoechst 33258 conjugate is reported. The conjugate combines the ligands known to selectively bind in the duplex and the triplex groove. The conjugate stabilizes DNA duplex over DNA triplex. The conjugate selectively stabilizes the DNA duplex (in the presence of salt), with as little as 2 muM of the ligand leading to a DeltaTm of 25 degrees C.

Triple-helical DNA can be formed by oligonucleotides that bind as third strands of DNA in a sequencespecific manner in the major groove in homopurine/homopyrimidine stretches in duplex DNA. Such triple helix-forming oligonucleotides have been used to inhibit gene expression by blocking transcription factor access to promoter sites in transient expression assays. In an alternative approach to ge...

Mycobacterium triplex, a recently described slowly growing nontuberculous mycobacterium, was isolated from a Finnish patient with pulmonary mycobacteriosis. The disease was successfully treated with antimycobacterial drugs. The strain isolated, which was similar to the type strain but differed slightly from the species description, was regarded as a variant of M. triplex sensu stricto. Accordin...

Gene targeting with DNA-binding molecules such as triplex-forming oligonucleotides or peptide nucleic acids can be utilized to direct mutagenesis or induce recombination site-specifically. In this chapter, several detailed protocols are described for the design and use of triplex-forming molecules to bind and mediate gene modification at specific chromosomal targets. Target site identification,...

The existence of sequences in the human genome which can be a target for triplex formation, and accordingly are candidates for anti-gene therapies, has been studied by using bioinformatics tools. It was found that the population of triplex-forming oligonucleotide target sequences (TTS) is much more abundant than that expected from simple random models. The population of TTS is large in all the ...

Triplexes are formed when a triplex-forming oligonucleotide (TFO), typically a short single stranded oligonucleotide recognizes a triplex-forming sequence (TFS) in a duplex DNA by means of specific hydrogen-bond interactions between the central Watson-Crick and the third nucleobase. Two types of triplexes exist: i) parallel triplexes based on the pyrimidine motif and Hoogsteen-type recognition ...

The development of new strategies for detecting microRNAs (miRNAs) has become a crucial step in the diagnostic field. miRNA profiles depend greatly on the sample and the analytical platform employed, leading sometimes to contradictory results. In this work, we study the use of modified parallel tail-clamps to detect a miRNA sequence involved in tumor suppression by triplex formation. Thermal de...

G-quadruplex (G4) can be formed by G-rich DNA sequences that are widely distributed throughout the human genome. Although G-triplex and G-hairpin have been proposed as G4 folding intermediates, their formation still requires further investigation by experiments. Here, we employed single-molecule FRET to characterize the folding dynamics of G4 from human telomeric sequence. First, we observed fo...

We have found that the bacterial transposon Tn7 can recognize and preferentially insert adjacent to triple-helical nucleic acid structures. Both synthetic intermolecular triplexes, formed through the pairing of a short triplex-forming oligonucleotide on a plasmid DNA, and naturally occurring mirror repeat sequences known to form intramolecular triplexes or H-form DNA are preferential targets fo...

The development of novel nucleoside analogues for the formation of triplex DNA containing pyrimidine-purine inversion sites has been a challenging field. In this paper, we describe the design and synthesis of non-natural nucleoside analogues, N-substituted-2'-deoxy-5-methylisocytidine derivatives, and their evaluation for triplex formation. It has been shown that N-(guanidinoethyl)-2'-deoxy-5-m...