Synthesis and Use of Modified Peptide Nucleic Acids for Visual Detection of DNA
[(S,S)-Trans-1,2-Cyclopentane Diamine-Modified and Gamma-Lysine-Modified-Peptide Nucleic Acids as Probes for Nucleic Acid Detection: Synthesis and Application]
Modification of peptide nucleic acids (PNAs) by the incorporation of trans-1,2-diaminocyclopentane into the PNA provides for more highly sensitive and selective detection of DNA and RNA sequences. The compounds disclosed in this invention have the potential for use in the development of nucleic acid detection kits for various pathogens.
Genomic analysis can provide key diagnostic information about the presence of pathogens or disease. At the present time DNA-based devices, such as DNA microarrays, are used for such an analysis. However, most of these analyses require the amplification of the DNA under investigation. Replacing the DNA probe with peptide nucleic acid (PNA) greatly facilitates the DNA detection because the binding strength of PNAs to complementary DNA is stronger than DNA binding to complementary DNA. Strong binding between PNA and DNA can eliminate the need for prior DNA amplification. Furthermore, PNAs bind to DNAs under low salt conditions, which disfavor formation of double-stranded DNA. By operating under low salt conditions, DNA can be denatured to ensure that target sequences are available for binding to a PNA probe. In addition, PNA is a synthetic molecule that cannot be broken down by enzymes, so the stability of PNAs allow for a device with a longer shelf life than one made from DNA. This technology also permits the presence of complementary DNA to be detected by eye (i.e. without instrumentation).
National Institutes of Health. April 2007.
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