Sequence-Universal Recognition of Duplex DNA by Oligonucleotides via Pseudocomplementarity and Helix Invasion (original) (raw)

2003, Chemistry & Biology

openers" for DNA duplexes [10-12], thus enabling hybridization of regular oligonucleotides and related probes with dsDNA via formation of so-called PD-loops [13][14][15]. One more approach, originally called "selective complementarity," is based on the pseudocomplementary strategy ) that makes it possible for a pair of mixed-base modified oligonucleotides to hybridize to dsDNA by strand invasion [16, 17]. Pseudocomplementarity means that two special derivatives of initially paired normal purine and pyrimidine are structurally ad-Summary justed in such a way that they (1) do not match each other but (2) are capable of a stable Watson-Crick-type The well-known Watson-Crick complementarity rules, pairing with the natural nucleobase complements (see which were discovered 50 years ago, elegantly direct for pseudocomplementary modified nucleothe specific pairing of two DNA single strands. On the bases we used). contrary, once formed, the double-stranded (ds) DNA Though robust, these approaches did not provide a lacks such a simple and sequence-universal recognifully satisfactory solution of the problem of dsDNA tartion principle, since most of the characteristic chemigeting by oligonucleotides. Indeed, mostly long oligocal groups of nucleobases are now buried deep inside purine tracts could presently be recognized via triplex the double helix, the major DNA form. We report a formation [6]. Although more general, the PD-looppromising versatile approach for highly selective recbased approach is still limited by purine-rich sequences ognition of designated sites within dsDNA featuring as well [11, 13]. On the other hand, the RecA-assisted considerable practical potential for a variety of molecsequence-unrestricted DNA recognition has much lower ular-biological, biotechnological, gene-therapeutic, specificity as compared to "pure" DNA-DNA (or DNAand diagnostic applications. It may also have implica-