Enhancement of selectivity in recognition of nucleic acids via chemical autoligation. |
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Authors: | S M Gryaznov R Schultz S K Chaturvedi R L Letsinger |
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Affiliation: | Lynx Therapeutics Inc., Hayward, CA 94545. |
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Abstract: | A new approach to increase the selectivity of interaction between oligonucleotide probes and target nucleic acids is described. In place of a single, relatively long oligonucleotide probe, two or three short oligomers terminated by thiophosphoryl and bromoacetamido groups are employed. Fast and efficient autoligation takes place when the oligomers hybridize in a contiguous mode to the same complementary strand such that a thiophosphoryl group on one strand and a bromoacetamido group on another are brought into proximity. A single nucleotide mismatch for the short probes leads to marked reduction in the rate of autoligation. The binding affinity of the product is close to that for a natural probe of the same length. This approach could have potential in oligonucleotide-based diagnostics, chemical amplification systems, and therapeutic applications. |
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