Peptide nucleic acid (PNA) is a synthetic analogue of DNA and RNA, developed more than a decade ago in which the naturally occurring sugar phosphate backbone has been replaced by the N-(2-aminoethyl) glycine units. Unlike DNA or RNA in the unhybridized state (single strand) which can adopt a helical structure through base-stacking, although highly flexible, PNA does not have a well-defined conformational folding in solution. Herein, we show that a simple backbone modification at the gamma-position of the N-(2-aminoethyl) glycine unit can transform a randomly folded PNA into a helical structure. Spectroscopic studies showed that helical induction occurs in the C- to N-terminal direction and is sterically driven. This finding has important implication not only on the future design of nucleic acid mimics but also on the design of novel materials, where molecular organization and efficient electronic coupling are desired.

One of the fundamental goals of molecular computing is to reproduce the tenets of digital logic, such as component modularity and hierarchical circuit design. An important step toward this goal is the creation of molecular logic gates that can be rationally wired into multi-level circuits. Here we report the design and functional characterization of a complete set of modular DNA-based Boolean logic gates (AND, OR, and AND-NOT) and further demonstrate their wiring into a three-level circuit that exhibits Boolean XOR (exclusive OR) function. The approach is based on solid-supported DNA logic gates that are designed to operate with single-stranded DNA inputs and outputs. Since the solution-phase serves as the communication medium between gates, circuit wiring can be achieved by designating the DNA output of one gate as the input to another. Solid-supported logic gates provide enhanced gate modularity versus solution-phase systems by significantly simplifying the task of choosing appropriate DNA input and output sequences used in the construction of multi-level circuits. The molecular logic gates and circuits reported here were characterized by coupling DNA outputs to a single-input REPORT gate and monitoring the resulting fluorescent output signals.

Defined broadly, molecular translators are constructs that can convert any designated molecular input into a unique output molecule. In particular, the development of universal nucleic acid translators would be of significant practical value in view of the expanding biomedical importance of gene diagnostics. Currently, diagnostic assays for nucleic acids must be individually developed and optimized for each new sequence because inputs for one assay are sequence-specific and are therefore incompatible with any other assay designed for the detection of a different nucleic acid. However, if a desired nucleic acid sequence could be translated in vitro into a predetermined nucleic acid output for which there is already a known diagnostic assay, then that single assay could be easily adapted to detect nearly any strand. Here we investigate PCR-independent isothermal molecular translation strategies that function without the need for post-translation purification and can be implemented with commercially available components. Translation yields up to 96% are obtained in 5 min at room temperature with minimal background reaction (<1%) and with discrimination of single nucleotide polymorphisms in the input sequence. Furthermore, we apply these translators to adapt a high-gain HIV diagnostic system for high-throughput detection of hepatitis C, avian influenza (H5N1), and smallpox without making changes to the underlying assay. Finally, we show the feasibility of translating small-molecule interactions into nucleic acid outputs by demonstrating the utility of a DNA aptamer for translating adenosine into a readily detectable output DNA sequence. Additionally, equilibrium expressions are described in order to facilitate rational engineering of aptameric translators for label-free detection of any molecule that an aptamer can recognize.

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