Abstract

Remarkable accomplishments demonstrating the importance of nucleic acids in molecular engineering and computation have been made over the past two decades. However, much of the work in this area so far has been carried out in vitro, utilizing almost exclusively homochiral D-DNAs (or D-RNAs) as chemical building blocks. Such natural building blocks are prone to enzymatic degradation and cross-hybridization with the host’s genetic materials. Here we report the development of an orthogonal nucleic acid system that is made up of a left-handed and a right-handed conformer, and a non-helical peptide nucleic acid analogue. We show that the stereochemical information inherent in the right-handed and left-handed conformers can be interconverted from (R) to (S) and vice versa, along with their helical sense and recognition capability, through strand displacement. The genetic information encoded in these synthetic building blocks can be interfaced with DNA or RNA through a molecular converter.

Highlights

  • Remarkable accomplishments demonstrating the importance of nucleic acids in molecular engineering and computation have been made over the past two decades

  • They are technically challenging to prepare and scale up for basic research consumption in comparison to the natural counterparts. Because of their recognition orthogonality, they cannot be directly interfaced. This latter issue has recently been addressed by Kabza and Sczepanski[37], in which they showed that the stereochemical information inherent in D-nucleic and L-nucleic acids can be interconverted by using peptide nucleic acid (PNA) as an interfacing medium

  • We report the phase of this investigation, demonstrating that the genetic information encoded in the RH and left-handed γPNA conformer (LH) conformers, as well as in natural nucleic acid biopolymers, can be interconverted through strand displacement

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Summary

Introduction

Remarkable accomplishments demonstrating the importance of nucleic acids in molecular engineering and computation have been made over the past two decades. Much of the work in this area so far has been carried out in vitro, utilizing almost exclusively homochiral D-DNAs (or D-RNAs) as chemical building blocks Such natural building blocks are prone to enzymatic degradation and cross-hybridization with the host’s genetic materials. The first two are orthogonal to each other in recognition, while the third is compatible with both the RH and LH conformers, as well as with DNA and RNA Unlike their natural counterparts, these chemical building blocks are impervious to enzymatic degradation[46]. The work has implications for the organization and assembly of materials and molecular computation in biological systems

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