Peptide Ribonucleic Acids (PRNA). 2. A Novel Strategy for Active Control of DNA Recognition through Borate Ester Formation

Abstract

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 the 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) backbone through the 5′-amino group. 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. Finally, it was unambiguously demonstrated that the γ-PRNA 8-mer with an isopoly-(L-glutamic acid) backbone can form a tight complex with DNA, and further, the recognition of DNA with γ-PRNA 8-mer is controlled by the borate added as an external factor.

Controlling the transmembrane transport of nucleosides

“…Chromatographic separation of sugars and nucleosides based on borate ester formation is well established (37) and lipophilic boronic acids have been used to facilitate transport of ribonucleosides across both liquid and liposomal membranes (12)(13)(14). Borate ester formation has been previously used to modulate the sugar conformation and consequent base-pairing properties of nucleic acid analogues in water (38). To our knowledge, formation of borate esters in water has not been used to modulate molecular transport across liquid membranes.…”

Structural Preorganization of Peptide Nucleic Acids: Chiral Cationic Analogues with Five- or Six-Membered Ring Structures

“…The strategy was further improved by the synthesis of isopoly--glutamic acid in which ribonucleoside units were attached as pendant groups through an amide linkage between the α-carboxy function of the glutamic acid and the 5Ј-amine of the ribonucleoside. This gave rise to the γ-peptide ribonucleic acid γ-PRNA (Figure 19 b), [61] in which the Eur. J. Org.…”

Synthesis of a thymine-functionalized nucleoamino acid for the solid phase assembly of cationic nucleopeptides

“…Several attempts to use real peptides as alternative oligonucleotide linkages have also been reported, leading to chiral nucleopeptides with useful characteristics (van der Laan et al 1998;Roviello et al 2009). Furthermore, examples of peptidelike analogs of DNA with long side chains able to form stable complexes with natural oligonucleotides of high sequence specificities were also reported in literature (Wada et al 2000;Sawa et al 2010).…”