Synthesis and Properties of the Simplified Nucleic Acid Glycol Nucleic Acid

摘要

Tnhe nucleosides of glycol nucleic acid (GNA), with the backbone comprising just the three carbons and one stereocenter of pro-npylene glycol (1,2-propanediol), probably constitute the simplest possible building blocks for a chemically stable nucleic acidnthat contains phosphodiester bonds. However, it was not until 2005 that the astonishing duplex formation properties of GNA homo-nduplexes were discovered in our laboratory. The R- and S-enantiomers of GNA, (R)-GNA and (S)-GNA, pair in like-symmetric com-nbinations to form highly stable antiparallel duplexes in a Watson Crick fashion, with thermal and thermodynamic stabilitiesnexceeding those of analogous duplexes of DNA and RNA. Interestingly, (R)-GNA and (S)-GNA do not significantly cross-pair withneach other, either in a parallel or antiparallel fashion. GNA discriminates strongly in favor of the Watson Crick base-pairing scheme,nwith only slightly lower fidelity than DNA. Two (S)-GNA homoduplex structures recently determined by X-ray crystallography, onena brominated 6-mer duplex and the other an 8-mer duplex containing two copper(II) ions, reveal that the overall GNA double helixnis distinct from canonical A- and B-form nucleic acids. The structure is perhaps best described as a helical ribbon loosely wrappednaround the helix axis. Within the backbone, the propylene glycol nucleotides adopt two different conformations, gauche and anti,nwith respect to the torsional angles between the vicinal C3′ O and C2′ O bonds. A strikingly large backbone base inclinationnresults in extensive zipper-like interstrand and reduced intrastrand base base interactions. This strong backbone base inclina-ntion might explain the observation that neither the R- nor S-enantiomer of GNA cross-pairs with DNA, whereas (S)-GNA can inter-nact with RNA strands that are devoid of G:C base pairs. Given the combination of structural simplicity, straightforward syntheticnaccessibility, and high duplex stability of GNA duplexes, GNA affords a promising nucleic acid scaffold for biotechnology and nano-ntechnology. Along these lines, we describe the functionalization of GNA duplexes through the incorporation of metal-ion-medi-nated base pairs. Finally, the properties of GNA discussed here reinforce its candidacy as one of the initial genetic molecules formednduring the origins of life on Earth.