Abstract:
Peptide nucleic acid (PNA) is a promising class of oligonucleotide analog with great potential for gene therapeutic applications. PNA is a DNA analog in which the normal phosphodiester backbone is replaced by acyclic, achiral and neutral amino-ethyl-glycyl (aeg) backbone. PNA can bind to complementary DNA/RNA sequence with high affinity and sequence specificity. PNA and its analogs are resistant to proteases and nucleases. Besides these advantages, PNA suffers from some limitations like low aqueous solubility, poor cell permeability and ambiguity in binding orientation. To overcome these limitations, in the present work, I have designed and synthesized PNA analog which has substitution at γ-C on the backbone. The substituted chain carries terminal cationic amino/guanidino group to improve binding affinity towards complementary DNA. The stability of PNA:DNA duplex is determined by temperature dependent UV spectroscopy. The γ -C modified PNA is shown to stabilize duplexes with complementary DNA better than the control unmodified PNA. The CD studies showed that the modification does not alter the conformation of PNA:DNA duplexes.
