Gamma Peptide Nucleic Acids: As Orthogonal Nucleic Acid Recognition Codes for Organizing Molecular Self-Assembly

J Am Chem Soc. 2015 Jul 8;137(26):8603-10. doi: 10.1021/jacs.5b04566. Epub 2015 Jun 29.


Nucleic acids are an attractive platform for organizing molecular self-assembly because of their specific nucleobase interactions and defined length scale. Routinely employed in the organization and assembly of materials in vitro, however, they have rarely been exploited in vivo, due to the concerns for enzymatic degradation and cross-hybridization with the host's genetic materials. Herein we report the development of a tight-binding, orthogonal, synthetically versatile, and informationally interfaced nucleic acid platform for programming molecular interactions, with implications for in vivo molecular assembly and computing. The system consists of three molecular entities: the right-handed and left-handed conformers and a nonhelical domain. The first two are orthogonal to each other in recognition, while the third is capable of binding to both, providing a means for interfacing the two conformers as well as the natural nucleic acid biopolymers (i.e., DNA and RNA). The three molecular entities are prepared from the same monomeric chemical scaffold, with the exception of the stereochemistry or lack thereof at the γ-backbone that determines if the corresponding oligo adopts a right-handed or left-handed helix, or a nonhelical motif. These conformers hybridize to each other with exquisite affinity, sequence selectivity, and level of orthogonality. Recognition modules as short as five nucleotides in length are capable of organizing molecular assembly.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alanine / chemistry
  • Amino Acid Motifs
  • Circular Dichroism
  • DNA / chemistry
  • Enzymes / chemistry
  • Macromolecular Substances
  • Nucleic Acid Conformation*
  • Nucleic Acid Hybridization
  • Peptide Nucleic Acids / chemistry*
  • Phosphates / chemistry
  • Polymers / chemistry
  • Polystyrenes / chemistry
  • Protein Structure, Tertiary
  • RNA / chemistry
  • Spectrophotometry, Ultraviolet
  • Stereoisomerism
  • Streptavidin / chemistry
  • Temperature
  • Thermodynamics


  • Enzymes
  • Macromolecular Substances
  • Peptide Nucleic Acids
  • Phosphates
  • Polymers
  • Polystyrenes
  • RNA
  • DNA
  • Streptavidin
  • Alanine
  • sodium phosphate