{'fraction_non_alphanumeric': 0.028604786923525978, 'fraction_numerical': 0.0011675423234092236, 'mean_word_length': 5.7215686274509805, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
A single-molecule insight into the ionic strength dependent, cationic peptide nucleic acids - oligonucleotides interactions.

To alleviate solubility-related shortcomings associated with the use of neutral peptide nucleic acids (PNA), a powerful strategy is incorporate various charged sidechains onto the PNA structure. Here we employ a single-molecule technique and prove that the ionic current blockade signature of free poly(Arg)-PNAs and their corresponding duplexes with target ssDNAs interacting with a single a-hemolysin (a-HL) nanopore is highly ionic strength dependent, with high salt-containing electrolytes facilitating both capture and isolation of such complexes. Our data illustrate the effect of low ionic strength in reducing the effective volume of free poly(Arg)-PNAs and augmentation of their electrophoretic mobility while traversing the nanopore.  We found that unlike in high salt electrolytes, the specific hybridization of cationic moiety-containing PNAs with complementary negatively charged ssDNAs in a salt concentration as low as 0.5 M is dramatically impeded. We suggest a scenario in which reduced charge screening by counterions in low salt electrolytes enables non-specific, electrostatic interactions with the anionic backbone of polynucleotides, thus reducing the ability of PNA-DNA complementary association via hydrogen bonding patterns. We applied an experimental strategy with spatially-separated poly(Arg)-PNAs and ssDNAs, and present evidence at the single-molecule level suggestive of the real-time, long-range interactions-driven formation of poly(Arg)-PNA-DNA complexes, as individual strands entering the nanopore from opposite directions collide inside a nanocavity.