A universal linker structure is provided, in which a functional group and
activating leaving group are placed on a tether, allowing the placement
of an electrophile at the end of any nucleic acid sequence. The
electrophile on the tether can react with a second nucleic acid carrying
a nucleophile when the two nucleic acids are hybridized near one another,
resulting in release of the leaving group, and creation of a functional
change. The linker can be designed to destabilize the ligation product
without slowing the rate of reaction. This lowers product inhibition, and
the target DNA or RNA can become a catalyst for isothermally generating
multiple signals for detection. This enhanced signal is demonstrated in
solution experiments and in solid supported assays. The universal linkers
of the present invention are simple and inexpensive to prepare, and can
be appended to any polynucleotide in automated steps on a standard DNA
synthesizer.