Functional Artificial Nucleic Acids: Peptide Ribonucleic Acids (Prnas) - Novel Strategy for Active Control of DNA Recognition by External Factors

The effect of adding borax and boric acids on the nucleobase orientation and recognition behavior of novel mono- and oligomeric peptide ribonucleic acids (PRNAs) has been investigated. The base orientation of 5'- amino-5'-deoxyuridine and 5'-amino-5'-deoxycytidine was shown by CD and NOE difference spectral studies to switch from anti to syn in borate buffer or upon addition of borax. The origin of this phenomenon is elucidated to be the cooperative effect of the cyclic borate esterification of sugar's cis-2',3'-diol and the hydrogen bonding interaction between the sugar's 5'-amino proton and the base's 2-carbonyl oxygen. Because this new strategy for switching the base orientation through the addition of borate is potentially applicable to the recognition control of nucleic acids if the sugar's 5'-proton and cis-2',3'-diol remain unmodified, we synthesized a series of PRNAs, in which the 5'-amino- 5'-deoxypyrimidine ribonucleoside moiety was appended to a mono- or oligo(γ-L-glutamic acid) and poly(α-L-glutamic acid) backbone through the 5'-amino group. The synthetic routes and procedures were established for all of the four fluorenemethyloxycarbonyl-protected PRNA monomers carrying uracil, N-benzoylcytosine, hypoxanthine, and N-benzoyladenosine nucleobases. Furthermore, a couple of PRNA 12-mers with desired purine-pyrimidine mixed sequences were prepared in high yields by the solid-phase synthesis. The orientation switching through the addition of borate was also confirmed with the monomeric model, and the switching efficiency was enhanced for oligomeric γ-PRNA. In case of the PRNA oligomer containing pyrimidinepurine mixed sequence, efficient orientational switching of nucleobases induced by added borates was observed. Finally, it was unambiguously demonstrated that the γ-PRNA oligomers with an isopoly(L-glutamic acid) backbone and poly the α-PRNA with poly(α-L-glutamic acid) backbone can form a tight complex with complementary DNA and/or RNA further the recognition of DNA with γ-PRNA oligomers and α-PRNA are controlled by the borate added as an external factor.