Benefits of γPNA

The Core Differences – γPNA vs. PNA Technology

The core technology of PNA Innovations is γPNA (gammaPNA). The original PNA structure, first reported by Nielsen, Egholm, Berg and Buchardt in 1991, consists of the natural nucleobases A, G, T and C connected to an unnatural extended peptide backbone. The lack of a negative charge on PNA contributes to high thermodynamic driving force for hybridization to complementary DNA and RNA. In some cases, PNA can even invade double stranded DNA in order to access its target sequence. The favorable hybridization properties for PNA have led to thousands of scientific publications and patents as well as commercialization of PNA technology in terms of monomers, custom oligomers, and specific products (e.g. FISH analysis of microorganisms).

γPNA represents an important step forward in the development of nucleic acid analogues. In 2006, Ly and coworkers demonstrated that incorporation of a substituent at the gamma carbon of the PNA backbone induces a helical structure in the molecule and that, depending on the chirality at the modified carbon, the molecule will adopt either a right- or left-handed helix. The right-handed version of γPNA exhibits exceptionally high affinity for complementary DNA and RNA targets, allowing invasion into virtually any double stranded target, regardless of sequence.

While the early work on γPNA focused on substituents found in natural amino acids, e.g. methyl (alanine), hydroxymethyl (serine), tetramethyleneammonium (lysine), a report in 2011 described a yPNA version in which the substituent was a mini-polyethylene glycol (miniPEG) group. This particular structure preserved the high affinity of the original γPNA structure, while significantly enhancing the solubility while eliminating aggregation, relative to unmodified PNA. Custom synthesized oligomers and other yPNA products sold by PNA Innovations are based on a proprietary structure that includes these miniPEG groups.

 

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