IP Library Granted Patent US 8,597,881
Granted Patent B2
US 8,597,881 · App. 13/281,275 · Granted Dec 3, 2013

Modified nucleotides

Inventors: John Milton (Nr. Saffron Walden, GB); Xiaolin Wu (Nr. Saffron Walden, GB); Mark Smith (Nr. Saffron Walden, GB); Joseph Brennan (Nr. Saffron Walden, GB); Colin Barnes (Nr. Saffron Walden, GB); Xiaohai Liu (Nr. Saffron Walden, GB); Silke Ruediger (Nr. Saffron Walden, GB)
Assignee: Illumina Cambridge Limited
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Quick Facts
Patent No.
US 8,597,881
App. No.
13/281,275
Granted
Dec 3, 2013
Kind
B2
Abstract

Provided herein is a method for replacing the allyl group in a compound of formula R—O-allyl, R 2 N(allyl), RNH(allyl), RN(allyl) 2 or R—S-allyl with a hydrogen, using a transition metal and one or more phosphine ligands.

Claims (15)

1. A method of converting a compound of formula R—O-allyl, R 2 N(allyl), RNH(allyl), RN(allyl) 2 or R—S-allyl to a corresponding compound in which the allyl group is removed and replaced by hydrogen, said method comprising the steps of reacting a compound of formula R—O-allyl, R 2 N(allyl), RNH(allyl), RN(allyl) 2 or R—S-allyl in aqueous solution with a transition metal comprising a transition metal and one or more ligands selected from the group comprising water-soluble phosphine and water-soluble nitrogen-containing phosphine ligands, wherein the or each R is a water-soluble biological molecule, which is part of a nucleoside, a nucleotide or a polynucleotide molecule, wherein said nucleoside, nucleotide or polynucleotide further comprises a detectable label linked to the base thereof by a cleavable or non-cleavable linker.

2. The method of claim 1 wherein said linker is cleavable.

3. The method of claim 1 wherein said detectable label is a fluorophore.

4. The method of claim 1 wherein said linker is acid labile, photolabile or contains a disulfide linkage.

5. The method of claim 1 wherein said allyl group and said label are removed in a single step.

6. The method of claim 1 wherein said transition metal is selected from the group comprising platinum, palladium, rhodium, ruthenium, osmium and iridium.

7. The method of claim 1 wherein said transition metal is palladium.

8. The method of claim 1 wherein said group of ligands comprise derivatised triaryl phosphine ligands or derivatised trialkyl phosphine ligands.

9. The method of claim 1 wherein said group of ligands are derivatised with one or more functionalities selected from the group comprising amino, hydroxyl, carboxyl and sulfonate groups.

10. The method of claim 1 wherein the group of ligands comprises 3,3′,3″-phosphinidynetris (benzenesulfonic acid) and tris(2-carboxyethyl)phosphines and their salts.

11. A method of converting a compound of formula R—O-allyl to a corresponding compound in which the allyl group is removed and replaced by hydrogen, said method comprising the steps of reacting a compound of formula R—O-allyl in aqueous solution with a transition metal comprising a transition metal and one or more ligands selected from the group comprising water-soluble phosphine and water-soluble nitrogen-containing phosphine ligands, wherein the R is a water-soluble biological molecule, which is part of a nucleoside, a nucleotide or a polynucleotide molecule, wherein said nucleoside, nucleotide or polynucleotide further comprises a detectable label linked to the base thereof by a cleavable or non-cleavable linker.

12. A method of converting a compound of formula R 2 N(allyl) to a corresponding compound in which the allyl group is removed and replaced by hydrogen, said method comprising the steps of reacting a compound of formula R 2 N(allyl) in aqueous solution with a transition metal comprising a transition metal and one or more ligands selected from the group comprising water-soluble phosphine and water-soluble nitrogen-containing phosphine ligands, wherein each R is independently a water-soluble biological molecule, which is part of a nucleoside, a nucleotide or a polynucleotide molecule, wherein said nucleoside, nucleotide or polynucleotide further comprises a detectable label linked to the base thereof by a cleavable or non-cleavable linker.

13. A method of converting a compound of formula RNH(allyl) to a corresponding compound in which the allyl group is removed and replaced by hydrogen, said method comprising the steps of reacting a compound of formula RNH(allyl) in aqueous solution with a transition metal comprising a transition metal and one or more ligands selected from the group comprising water-soluble phosphine and water-soluble nitrogen-containing phosphine ligands, wherein the R is a water-soluble biological molecule, which is part of a nucleoside, a nucleotide or a polynucleotide molecule, wherein said nucleoside, nucleotide or polynucleotide further comprises a detectable label linked to the base thereof by a cleavable or non-cleavable linker.

14. A method of converting a compound of formula RN(allyl) 2 to a corresponding compound in which the allyl group is removed and replaced by hydrogen, said method comprising the steps of reacting a compound of formula RN(allyl) 2 in aqueous solution with a transition metal comprising a transition metal and one or more ligands selected from the group comprising water-soluble phosphine and water-soluble nitrogen-containing phosphine ligands, wherein the R is a water-soluble biological molecule, which is part of a nucleoside, a nucleotide or a polynucleotide molecule, wherein said nucleoside, nucleotide or polynucleotide further comprises a detectable label linked to the base thereof by a cleavable or non-cleavable linker.

15. A method of converting a compound of formula R—S-allyl to a corresponding compound in which the allyl group is removed and replaced by hydrogen, said method comprising the steps of reacting a compound of formula R—S-allyl in aqueous solution with a transition metal comprising a transition metal and one or more ligands selected from the group comprising water-soluble phosphine and water-soluble nitrogen-containing phosphine ligands, wherein the R is a water-soluble biological molecule, which is part of a nucleoside, a nucleotide or a polynucleotide molecule, wherein said nucleoside, nucleotide or polynucleotide further comprises a detectable label linked to the base thereof by a cleavable or non-cleavable linker.

Assignments (2)
CHANGE OF NAME Recorded Nov 30, 2011
From: SOLEXA LIMITED
To: ILLUMINA CAMBRIDGE LIMITED
Reel/Frame 027299/0760 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 30, 2011
From: MILTON, JOHN; WU, XIAOLIN; SMITH, MARK; BRENNAN, JOSEPH; BARNES, COLIN; LIU, XIAOHAI; RUEDIGER, SILKE
To: SOLEXA LIMITED
Reel/Frame 027305/0137 →
Priority Claims (2)
GB 0230037.4 · Dec 23, 2002 · national
GB 0303924.5 · Feb 20, 2003 · national
Continuity (4)
Division 12804352 · Jul 20, 2010
Division 12455397 · Jun 1, 2009
Division 10525401
Related Publication 20120095201A1 · Apr 19, 2012