Exiqon A/s

Henrik M Pfundheller

Jef Fensholdt

Alexei Kochkine

Christian Lomholt

Michael Meldgaard

The present invention provides novel quencher composition comprising anthraquinone quencher moieties. The anthraquinone quencher moieties are useful as quencher labels when attached to biomolecules such as natural or modified polynucleotides, oligonucleotides, nucleosides, nucleotides, carbohydrates and peptides. For example, polynucleotides can be labeled at the 3' terminus with fluorescence quencher solid support compositions, and polynucleotides can be labeled at internally or at the 5&#x2032; terminus. The detectable probes may have a format like molecular beacons, scorpion probes, sunrise probes, conformationally assisted probes and TaqMan probes.

Quencher compositions comprising anthraquinone moieties

A synthesis of &lsqb;2.2.1&rsqb;bicyclo nucleosides which is shorter and provides higher overall yields proceeds via the key intermediate of the general formula III, wherein R and R are, for instance, sulfonates and R is, for instance, a halogen or an acetate. From compounds of the general formula II, such as 3-O-aryl-4-C-hydroxymethyl-1,2-O-isopropylidene-&agr;-D-ribofuranose, intermediates of the general formula III are suitable for coupling with silylated nucleobases. Upon one-pot base-induced ring-closure and desulfonation of the formed &lsqb;2.2.1&rsqb;bicyclo nucleoside, a short route to each the LNA (Locked Nucleic Acid) derivatives of adenosine, cytosine, uridine, thymidine and guanidine is demonstrated. The use of the 5&prime;-sulfonated ring-closed intermediate also allows for synthesis of 5&prime;-amino- and thio-LNAs

Synthesis of &lsqb;2.2.1&rsqb;bicyclo nucleosides

A synthesis of &lsqb;2.2.1&rsqb;bicyclo nucleosides which is shorter and provides higher overall yields proceeds via the key intermediate of the general formula III, wherein R and R are, for instance, sulfonates and R is, for instance, a halogen or an acetate. From compounds of the general formula II, such as 3-O-aryl-4-C-hydroxymethyl-1,2-O-isopropylidene-&agr;-D-ribofuranose, intermediates of the general formula III are suitable for coupling with silylated nucleobases. Upon one-pot base-induced ring-closure and desulfonation of the formed &lsqb;2.2.1&rsqb;bicyclo nucleoside, a short route to each the LNA (Locked Nucleic Acid) derivatives of adenosine, cytosine, uridine, thymidine and guanidine is demonstrated. The use of the 5&prime;-sulfonated ring-closed intermediate also allows for synthesis of 5&prime;-amino- and thio-LNAs.

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Frederiksberg, Denmark

Henrik M Pfundheller