Gamma/ Bis PNA
Homopyrimidine PNA bind to complementary DNA forming (PNA)2/DNA triplexes of very high thermal stability via strand displacement instead of conventional triple helix formation. The most stable (PNA)2/DNA triplex is formed when the Watson-Crick base pairing PNA strand is in the anti-parallel orientation relative to the DNA strand and the Hoogsteen strand is in the parallel orientation relative to the DNA strand. Bis-PNA contains pseudoisocytosine (J) instead of cytosine (C) in the “Hoogsteen strand” can efficiently bind double strand DNA in a pH independent manner.
Bis PNA binding is presently limited to mostly homopurine and homopyrimidine stretches while gamma PNA can be an alternative that can be more flexible with target sequence selection.
Gamma PNA has a stereogenic center at the γ-carbon atom of the N-aminoethylglycine unit. γ-substituted PNA can be placed in every third residue of regular PNA.
Tm of gammaPNA is higher by 5~8 ℃ per single substitution, which result in more sequence specific binding at higher affinity. In addition, gamma PNA can invade double stranded DNA to form a triple helix.
Moreover,gamma PNA can provide several advantages such as improved solubility, less self-aggregation, more stable PNA-DNA duplexe formation, and flexibility for multi labeling and other functionalization.
- Lysine: better solubility, possible for dual labeling, potential for cell penetration
- MiniPEG: best for improved solubility and specific binding, efficient for double strand DNA invasion
- Alanine and glutamic acid are also possible modification.
- Nanopore-Based Target Sequence Detection. Morin TJ et al (2016)PLoS One 11(5):e0154426.
- Single-stranded γPNAs for in vivo site-specific genome editing viaWatson-Crick recognition. Bahal R et al (2015) Curr Gene Ther 14(5):331-342.
- Site-specific genome editing in PBMCs With PLGA nanoparticle-delivered PNAs confers HIV-1 resistance in humanized mice. Schleifman EB et al (2013) Mol Ther Nucleic Acids 2:e135.
- Sequence-unrestricted, Watson-Crick recognition of double helical B-DNA by (R)-miniPEG-γPNAs. Bahal R et al (2012) Chembiochem 13(1):56-60.
- Quadruplex formation is necessary for stable PNA invasion into duplex DNA of BCL2 promoter region. Onyshchenko MI et al (2011) Nuc Acids Res 39(16):7114-23.
- Strand-invasion of extended, mixed-sequence B-DNA by γPNAs. He G et al (2010) J Am Chem Soc 131(34):12088-90.
- PNA-dependent gene chemistry: stable coupling of peptides and oligonucleotidesto Plasmid DNA. Zelphati O et al (2000) Biotech 28(2)304-315.
- Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA. Egholm M et al (1995) Nuc Acid Res 23(2):217-111.
Custom PNA oligos provided by PNA Bio will be provided >95% purity, accompanied by COA including HPLC and mass data. Synthesis usually takes 3~4 weeks for bis PNA or gamma PNA.
The price of custom oligo is dependent on the length, amount and label. Please indicate the specifics in quote request. Feel free to check out PNA Tool for Tm calculation and other guidelines for PNA design.
Minimum amount is 50 nmole for non-labeled PNA and 25 nmole for labeled PNA.
Please send quote request and order to firstname.lastname@example.org or click here for inquire. We can also help the design of bis PNA or gamma PNA.