Mapping the Landscape of Potentially Primordial Informational Oligomers: Oligodipeptides and Oligodipeptoids Tagged with Triazines as Recognition Elements

Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Angewandte Chemie International Edition (Impact Factor: 11.34). 03/2007; 46(14):2470-7. DOI: 10.1002/anie.200603207
Source: PubMed
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report herein DNA and RNA templated chemical transformation of bifacial peptide nucleic acid (bPNA) fragments directed by an abiotic triplex hybrid interface. Assembly of one bPNA strand with two unstructured oligo T/U strands enables facile insertion of DNA and RNA template sites within partially folded nucleic acids; this template topology is not easily accessed through native base pairing. Triplex hybridization of reactive bPNA fragments on DNA and RNA templates is shown to catalyze amide bond ligation and controlled bPNA chain extension. RNA templated oxidative coupling of bPNA fragments is found to result in the emergence of ribozyme cleavage function, thus establishing a connection between engineered and native reaction sites. These data demonstrate the use of new topologies in nucleic acid templated chemistry that could serve as chemically sensitive DNA and RNA switches.
    Journal of the American Chemical Society 03/2015; 137(11). DOI:10.1021/jacs.5b00236 · 11.44 Impact Factor
  • Source
    Chemical Reviews 10/2013; 114(1). DOI:10.1021/cr2004844 · 45.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We demonstrate herein that bifacial peptide nucleic acid (bPNA) hybrid triplexes functionally substitute for duplex DNA or RNA. Structure–function loss in three non-coding nucleic acids was inflicted by replacement of a duplex stem with unstructured oligo-T/U strands, which are bPNA binding sites. Functional rescue was observed on refolding of the oligo-T/U strands into bPNA triplex hybrid stems. Bifacial PNA binding was thus used to allosterically switch-on protein and small-molecule binding in DNA and RNA aptamers, as well as catalytic bond scission in a ribozyme. Duplex stems that support the catalytic site of a minimal type I hammerhead ribozyme were replaced with oligo-U loops, severely crippling or ablating the native RNA splicing function. Refolding of the U-loops into bPNA triplex stems completely restored splicing function in the hybrid system. These studies indicate that bPNA may have general utility as an allosteric trigger for a wide range of functions in non-coding nucleic acids.
    Journal of the American Chemical Society 05/2014; 136(20):7265–7268. DOI:10.1021/ja5032584 · 11.44 Impact Factor