Enhancement of selectivity in recognition of nucleic acids via chemical autoligation.
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.
Lynx Therapeutics Inc., Hayward, CA 94545.
S M
SM
Gryaznov
R
R
Schultz
S K
SK
Chaturvedi
R L
RL
Letsinger
D001482:Base Composition; D002851:Chromatography, High Pressure Liquid; D005821:Genetic Techniques; D009696:Nucleic Acids / Q000032:analysis*; D015345:Oligonucleotide Probes
D009696:Nucleic Acids; D015345:Oligonucleotide Probes