Proposed herein is the synthesis of several uncharged stereoregular polynucleotide analogs consisting of heterocyclic bases linked at specific intervals to linear backbones. Molecular modeling studies suggest these analogs will pair in a sequence-specific manner via Watson/Crick bonds to complementary polynucleotides. Following synthesis, these polynucleotide analogs will be assessed for their ability to pair with specific polynucleotide sequences. Pairing specificities and avidities will be studied by measuring UV absorbance versus temperature, by spectrophotometric mixing curves, and by equilibrium dialysis. Finally, structures of the analog/polynucleotide complexes will be studied by high resolution NMR spectroscopy. Because of their uncharged backbones, these polynucleotide analogs should have the useful properties of a) pairing with complementary polynucleotides in low salt conditions wherein annealing between complementary polynucleotides is precluded and b) not binding substances which bind electrostatically to polynucleotide backbones. These special properties make the proposed analogs ideal for use in a new diagnostic system which is easily automated, simple, fast, cheap, and several orders of magnitude more sensitive than current DNA probe-based systems. These uncharged polynucleotide analogs may also have other valuable applications, including: in vivo inactivation of viruses having single-stranded genomes; and, in vivo inactivation of specific messenger RNAs.
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