Heterogeneous Pyrophosphate-Linked DNA-Oligonucleotides: Aversion to DNA but Affinity for RNA.

Pyrophosphate linkages are important in extant biology and are hypothesized to have played a role in prebiotic chemistry and in the origination of oligonucleotides. Inspired by pyrophosphate as backbones of primordial oligomers, DNA oligomers with varying amounts of pyrophosphate inserts (ppDNA) were synthesized and investigated for their base-pairing properties. As expected, pyrophosphate inserts into the backbone compromised the thermal stability of ppDNA-DNA duplexes. In contrast, the ppDNA-RNA duplex exhibited, remarkably, duplex stability, even with accumulation of pyrophosphate linkages. This seems to be a consequence of an increase in the diameter of the double-helix with eight-bond-repeat units, and higher inclination of the base-pair axis with respect to the backbone in RNA (A-form), compared with that in DNA (B-form). These results suggest that pyrophosphate-linked oligonucleotides could harbor functional capabilities with implications for their roles in the origins of life and chemical biology.