Backbone extended pyrrolidine PNA (bepPNA): a chiral PNA for selective RNA recognition

Synthesis of cationic, chiral PNA analogues with an extra atom in the backbone (bepPNA) is reported. The (2S,4S) geometry of the pyrrolidine ring, and an additional carbon atom in the backbone of homopyrimidine-bepPNAs resulted in the optimization of the inter-nucleobase distance, such that selective binding to complementary RNA over DNA was observed in the triplex mode. It was evident from circular dichroism studies that oligomers with mixed aminoethylglycyl–bep (aeg–bep) repeating units, and also bepPNA with homogeneous backbone attained structures quite different from those of aegPNA2:RNA/DNA complexes. The bepPNA, when incorporated in a duplex forming mixed purine–pyrimidine sequence, also showed a preference for binding complementary RNA over DNA.