Enantiomeric Selection Properties of P-homoDNA: Enhanced Pairing for Heterochiral Complexes

摘要

The analysis of the physicochemical properties of sugar-modified nucleic acids is currently at the core of intense multidisciplinary investigations including chemistry, biology, biotechnology, and medicine. On one side, synthetic polymers acting as RNA/DNA mimics have extensively been devised for applications in therapy, diagnostics, and synthetic biology.On the other side, the construction of alternative pairing systems has been explored either to consider their use as orthogonal nucleic acid candidates or with the aim to potentially yield insights into the chemical evolution criteria ultimately leading to the current genetic system. In all cases, structural changes of natural (deoxy)ribose cores have been established to determine profound consequences in the pairing potential of the resulting artificial nucleic acids. In some noteworthy examples, oligonucleotide systems endowed with six-membered sugars in the backbone have been observed to hold the singular property (unique of its kind) of pairing with homochiral complements having opposite sense of chirality. Relevant to etiology-oriented investigations on nucleic acid structure, these findings could suggest the existence of a relationship between nature of the sugar backbone and chiral-selection properties of nucleic acids, thereby providing insights to enrich our understanding of the structural prerequisites for base pairing. From a comparative analysis of the pairing behavior of six-membered nucleic acids weperceived that, despite the large structural differences, oligonucleotide systems capable of iso- and heterochiral hybridization (Figure 1) shared preor-ganized carbohydrate conformations with equatorially-ori-ented nucleobases.