Detection of nucleic acids by fluorescence quenching

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

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435 912, 536 243, 536 253, 536 2532, C12Q 168, C12P 1934, C07H 2104

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059587008

ABSTRACT:
A detector oligonucleotide having a sequence which forms an intramolecularly base-paired secondary structure is described for use in detecting nucleic acid target sequences and target sequence amplification. The detector oligonucleotide is further modified by linkage to two dyes which form a donor/acceptor dye pair. The two dyes are positioned on the detector oligonucleotide such that they are in close spatial proximity in the base-paired, folded secondary structure, thereby causing quenching of donor fluorescence. The detector oligonucleotide may optionally further comprise a restriction endonuclease recognition site (RERS) which remains partially or entirely single-stranded in the base-paired secondary structure. The RERS is flanked by the two dyes. In the presence of target, the base-paired secondary structure is unfolded or linearized, increasing the distance between the donor and acceptor dyes and causing a change in fluorescence of the donor and/or the acceptor. If an RERS is present, it is rendered double-stranded in the presence of target, allowing cleavage or nicking by a restriction endonuclease and separation of the two dyes onto separate nucleic acid fragments. This may further contribute to the magnitude of the change in fluorescence.

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L. E. Morrison "Detection of Energy Transfer and Fluorescence Quenching" Nonisotopic DNA Probe Techniques Academic Press, pp. 311-352 (1992).
S. S. Ghosh, et al. "Real time kinetics of restriction endonuclease cleavage monitored by fluorescence resonance energy transfer" Nucl. Acids Res. 22:3155-3159 (1994).
L. G. Lee, et al. "Allelic discrimination by nick-translation PCR with fluorogenic probes" Nucl. Acids Res. 21:3761-3766 (1993).
S. P. Lee, et al. "A Fluorometric Assay for DNA Cleavage Reactions Characterized with BamHl Restriction Endonuclease" Anal. Biochem. 220:377-383 (1994).

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