Additional Funding Sources
The project described was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant No. P20GM103408.
Abstract
Nucleic acid (NA) mimics show promise for sequence-unrestricted recognition of double-stranded (ds) DNA, which in turn has exciting prospects for diagnostics and treatment of genetic diseases. Invader probes are examples of NA mimics, first introduced by the Hrdlicka Lab. These short DNA duplexes are highly modified with so-called +1 interstrand zipper arrangements of 2′-O-(pyren-1-yl)methyl-RNA monomers. Locked Nucleic Acids (LNAs) are another class of NA mimics that feature a conformationally restricted sugar ring. Here, chimeric double-stranded probes between Invader and LNA strands are studied based on premise that the chimeras will be labile, whereas each probe strand has high affinity towards complementary DNA (cDNA). Chimeric LNA-Invader probes are synthesized and characterized with respect to purity and thermal denaturation properties. Here, we report how troubleshooting events provide room for optimal synthesis and application of chimeric LNA-Invader probes.
Recognition of DNA Using Fully Modified Chimeric LNA-Invader Probes
Nucleic acid (NA) mimics show promise for sequence-unrestricted recognition of double-stranded (ds) DNA, which in turn has exciting prospects for diagnostics and treatment of genetic diseases. Invader probes are examples of NA mimics, first introduced by the Hrdlicka Lab. These short DNA duplexes are highly modified with so-called +1 interstrand zipper arrangements of 2′-O-(pyren-1-yl)methyl-RNA monomers. Locked Nucleic Acids (LNAs) are another class of NA mimics that feature a conformationally restricted sugar ring. Here, chimeric double-stranded probes between Invader and LNA strands are studied based on premise that the chimeras will be labile, whereas each probe strand has high affinity towards complementary DNA (cDNA). Chimeric LNA-Invader probes are synthesized and characterized with respect to purity and thermal denaturation properties. Here, we report how troubleshooting events provide room for optimal synthesis and application of chimeric LNA-Invader probes.