Helical sense preference in peptide nucleic acid duplexes

Helical handedness has been found to be influenced with a chiral amplification mechanism, which could be studied in quantitative detail in a model system, the polyisocyanates and found to be limited by the intervention of helical reversals. Due to the lack of hydrogen bonding and other physical interactions as is the situation in biological molecules such as DNA, RNA or alpha-helical proteins which stabilize the helical structures, the tendency to undergo a helical reversal in the synthetic polymers is more facile.; We have extended our studies on chiral amplification limited by helical reversals in helical polymers to a DNA mimic - peptide nucleic acids (PNAs). PNAs are synthetic variants of DNA, carrying a peptide backbone in place of the sugar phosphate backbone of DNA molecules. As a result, PNAs can efficiently base pair with DNA as well as RNA molecules as per the Watson Crick rules. Interestingly, however, they are resistant to degradation by nucleases and peptidases. Due to these properties, PNAs are emerging as very promising tools for antigene and antisense therapy to cure various genetic disorders.; It has been reported by Nielsen that an amino acid such as L-lysine at the carboxy terminus of one of the PNA strands induces a preferred handedness in a PNA-PNA duplex. Using circular dichroism spectroscopy it was reported that the amino acid has its effect up to 10 base pairs after which the CD signal reaches a limit. We have extended studies on this system to higher oligomer lengths, 6-mer up to 19-mer, and found that lysine asserts a similar helical sense preference, independent of the oligomer chain length at room temperature. However, a hint of a drop in the molar ellipticities per residue is seen especially for the 19-mer PNA duplex. Our studies eliminate the possibility of helical reversals within a duplex, even at higher temperatures and for the longer duplexes.; We have extended this work to study the effect of glycerol on the stabilities of these PNA-PNA duplexes. It has been reported that glycerol tends to weaken the DNA-DNA duplex by reducing the dielectric constant of water thereby increasing the electrostatic repulsions between the negatively charged DNA strands. The PNAs being inherently neutral should therefore have been stabilized in glycerol an expectation realized in our experimental results.; PNA duplexes were also studied in the presence of other alcohols such as methanol, ethanol and isopropanol. Our interest for studying the PNA duplexes in various solvents other than water was to gain possible insight into the structure of the DNA duplex parallel to the studies in glycerol mentioned above. We found that in the presence of these alcohols the various PNAs adopt different structural features as in case of the DNA duplex. However the structure adopted by PNAs in the presence of these alcohols does not correspond to either of the A-, B- or C-form DNA as mentioned in the literature.