Poster abstracts

Poster number 167 submitted by Sharon Wu

Gamma Peptide Nucleic Acids as a Platform for Orthogonal Nucleic Acid Recognition Codes

Ashley Wang (Department of Chemistry, Carnegie Mellon University), Sharon Wu (Department of Chemistry, Carnegie Mellon University), Iulia Sacui, Wei-Che Hsieh (Department of Chemistry, Carnegie Mellon University), Arunava Manna (Department of Chemistry, Carnegie Mellon University), Bichismita Sahu (Department of Chemistry, Carnegie Mellon University), Danith H. Ly (Department of Chemistry, Carnegie Mellon University)

Abstract:
Nucleic acids have recently shown great promise in nanotechnology, including advances in molecular computing and assembly. The assembly of nucleic acids can be rationally designed and synthesized through knowledge and programmability of their thermodynamic behaviors and 3D structures. However, enzymatic degradation and cross-hybridization with the host genome present barriers for the further exploitation of nucleic acids in in-vivo studies. Such complications can be addressed with the use of peptide nucleic acid (PNA), a synthetic analogue of DNA and RNA which displays resistance towards enzymatic degradation and shows high sequence specificity. Our previous studies found that a simple backbone modification at the γ-position of the N-(2-aminoethyl) glycine unit preorganized the γ-PNA into a right handed (RH) helical motif, making γ-PNA more thermodynamically favorable for binding to complementary sequences (Bahal et al., 2012, Sahu et al., 2011). In our present work, we found that by switching the stereochemistry of the γ-position substituent, a mirror image of the RH molecule was produced. Circular dichroism studies revealed the γ-PNA adopted a left-handed (LH) helical sense. UV melting and fluorescent studies demonstrated that LH γ-PNA cannot hybridize to RH γ-PNA, DNA or RNA, classifying this new PNA as being orthogonal to the others. Furthermore, UV melting studies show that given the same base sequences but different helical senses, LH and RH γ-PNA have similar binding affinities toward their complementary sequences, allowing us to predict the thermodynamic properties of LH γ-PNA. More interestingly, without the γ-substituent, PNA adopted a nonhelical (NH) motif, allowing the NH PNA to act as an interface between LH γ-PNA and RH γ-PNA. These three moieties constitute a new platform for recognizing and manipulating endogenous genomic material, which can open up to new opportunities for in-vivo molecular self-assembly and computing.

References:
I. Sacui, W.-C. Hsieh, A. Manna, B. Sahu, and D. H. Ly, "Gamma peptide nucleic acids:
As orthogonal nucleic acid recognition codes for organizing molecular self-assembly",
J. Am Chem. Soc. 2015, 137, 8603.

B. Sahu, I. Sacui, S. Rapireddy, K. J. Zanotti, R. Bahal, B. A. Armitage, and D. H. Ly, “Synthesis and characterization of conformationally preorganized, (R)-diethylene glycol-containing γ-peptide nucleic acids with superior hybridization properties and water solubility”, J. Org. Chem. 2011, 76, 5614.

R. Bahal, B. Sahu, S. Rapireddy, C. M. Lee, and D. H. Ly, “Sequence-Unrestricted, Watson–Crick Recognition of Double Helical B-DNA by (R)-MiniPEG-γPNAs”, ChemBioChem. 2012, 13, 56.

Keywords: Peptide nucleic acid, Molecular self-assembly, Molecular computing