For decades, scientists have pursued synthesis of artificial forms of DNA, such as bio-identical synthetic nucleotide oligomers and more recently, DNA mimetics such as peptide nucleic acids (PNA). Synthetic peptide nucleic acids are used in a variety of applications including molecular biology procedures, such as nucleic acid purification, PCR detection of mutant DNA sequences using PNA clamps, PNA FISH probes for diagnostic assays, detection of genetically modified organisms in food using PNA microarrays combined with PCR and in antisense gene therapy. While scientists have successfully synthesized such peptides and oligomers, the synthesis is costly and complex due in part to the need for solid-phase synthesis. Other disadvantages of PNAs include, need for large reactant excesses, slow reaction kinetics, and concerns pertaining to side reactions, formation reactions, and also the peptidic backbone. Thus, there is a need for novel nucleic acid mimetics.
A research team led by Dr. Christopher Bowman of the University of Colorado has developed a novel DNA analog identified as click nucleic acids (CNA). Sequences of CNA are synthesized using click chemistry in a radical mediated thiol-ene reaction. This reaction can be performed under mild conditions and is characteristically simple and robust with few side reactions. The nature of the click chemistry reaction allows the production of larger quantities of CNA at a greatly reduced cost. Similarly to PNA, CNA is capable of mimicking the DNA property to specifically associate with complimentary nucleic acid materials, including DNA, RNA, and PNA, but with greater binding specificities and selectivities. We anticipate that CNA can be utilized in all applications currently utilizing DNA, RNA, and PNA, such as anti-sense gene therapeutics, bio-detection, genomic arrays, nanoscale devices, and nucleic acid-based origami among others.