Polypurine reverse-Hoogsteen hairpin

The two polypurine domains interact by intramolecular reverse-Hoogsteen bonds allowing the formation of this specific hairpin structure.

PPRHs present high stability in serum and cells and show lack of immunogenicity not activating the innate inflammatory response.

Their action has been demonstrated in vitro for a number of genes involved in metabolism (DHFR), proliferation (mTOR), DNA topology (TOP1), lifespan and senescence (telomerase), apoptosis (survivin, BCL2), transcription factors and non-druggable targets (c-MYC[7] and k-Ras[8]) , proto-oncogenes (MDM2),[9] replication stress (WEE1, CHK1)[10] and Thymidilate synthase (TYMS)[11] as part of a cancer gene therapy strategy.

[14][15] PPRHs can also be used as the capture probe in different devises to detect viral infection by forming a triplex with the RNA of the virus such as SARS-CoV-2 in a technology termed Triplex Enhanced Nucleic Acid Detection Assay (TENADA)[16] PPRHs can be designed for virtually any gene in the genome by searching for polypirimidine stretches in the sequence of the desired gene.

Integrative WEB tools for identification and analysis of the triplex formation target DNA sequences, including PPRH sequences, associated with genes and regulatory elements (e.g., transcription factor binding sites, repeats, G-quadruplet motifs, SNPs, and non-protein coding regulatory DNA elements) in the human genome are publicly available (see External links).

PPRH structure showing the two homopurine domains bound by Reverse Hoogsteen bonds
Template-PPRHs bind to the template strand of the dsDNA. Coding-PPRHs bind to the coding strand of the dsDNA
Wild type-PPRH: Version of PPRH containing a pyrimidine in front of purine interruptions in the DNA target.
Wedge-PPRH: Specific type of PPRH with an extension on the 5' end bearing the complementary sequence of the displaced strand of the target dsDNA