| The ultimate aim of this research project is the development of a new class of nucleic acid surrogates, capable of sequence specific recognition of single stranded DNA and RNA as well as double stranded DNA targets. The combination of the key elements of “protein structure” and “nucleic acid functions” will be present in these surrogates.; An entirely new class of such surrogates was designed by a merger of the α-helix (protein's structural feature) and nucleobases (nucleic acid's functional element), which are named as α-helical peptide nucleic acids or αPNAs. Nucleobases are attached to the side chains of amino acids at regular intervals in an α-helix to generate such hybrid structures. These regularly placed nucleobases will participate in the sequence specific recognition of complementary strands of nucleic acids.; The successful synthesis of the nucleoamino acid building blocks, which are necessary to synthesize the αPNAs, was demonstrated. An optimized solid phase synthesis protocol to assemble these nucleoamino acids (along with the other three amino acids) into αPNAs was established. The first generation (backbone1, b1) αPNAs are composed of an amino acid sequence that inherently favors helix formation and are essentially helical in solution, while the second generation (backbone2, b2) αPNAs are cationic. These b1 & b2 αPNAs bind with ssDNAs strongly and sequence specifically. The rate of binding of b1 αPNAs with ssDNAs is slower compared to b2. After complexation with ssDNA, b2 αPNAs fold into an α-helix. Also, monomeric αPNAs form complexes with ssDNAs in a one to one ratio. Finally, the orientation of αPNA (parallel/anti-parallel) with respect to the ssDNA after complexation affects the affinity and nature of binding. |
