IP Library › Granted Patent US 7,491,818
Granted Patent B2
US 7,491,818 · App. 11/037,065 · Granted Feb 17, 2009

Nucleic acid labeling compounds

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Quick Facts
Patent No.
US 7,491,818
App. No.
11/037,065
Granted
Feb 17, 2009
Kind
B2
Abstract

Nucleic acid labeling compounds containing heterocyclic derivatives are disclosed. The heterocyclic derivative containing compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.

Claims (109)

1. A nucleic acid labeling compound comprising the formula:

wherein A is H or a functional group that permits the attachment of the nucleic acid labeling compound to a nucleic acid;

X is O, S, NR 1 , or CHR 2 , wherein R 1 and R 2 are, independently, H, alkyl or aryl;

Y is H, N 3 , F, OR 9 , SR 9 or NHR 9 , wherein R 9 is H, alkyl or aryl;

Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl;

L is amino alkyl;

Q is a detectable moiety; and

M is a connecting group, wherein m is an integer ranging from 0 to about 3.

2. A nucleic acid labeling compound according to claim 1 , wherein A is H or H 4 O 9 P 3 —; X is O; Y is H or OR 9 , wherein R 9 is H, alkyl or aryl; Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl; L is —NH(CH 2 ) n NH—, wherein n is an integer ranging from about 2 to about 10; Q is biotin or carboxyfluorescein; and M is —CO(CH 2 ) 5 NH— or —CO(CH 2 ) 5 NHCO(CH 2 ) 5 NH—, wherein m is 1 or 0.

3. A nucleic acid labeling compound according to claim 2 , wherein Y is H or OH; Z is H or OH; L is —NH(CH 2 ) 4 NH—; Q is biotin; and M is —CO(CH 2 ) 5 NH—, wherein m is 1.

4. A nucleic acid labeling compound according to claim 2 , wherein Y is H or OH; Z is H or OH; L is —NH(CH 2 ) 4 NH—; Q is 5-carboxyfluorescein; and M is —CO(CH 2 ) 5 NH—, wherein m is 1.

5. A nucleic acid labeling compound according to claim 2 , wherein A is H; Y is OH; Z is OH; L is —NH(CH 2 ) 4 NH—; Q is biotin; and M is —CO(CH 2 ) 5 NH, wherein m is 1.

6. A nucleic acid labeling compound according to claim 2 , wherein A is H 4 O 9 P 3 —; Y is OH; Z is OH; L is —NH(CH 2 ) 4 NH—; Q is biotin; and M is —CO(CH 2 ) 5 NH, wherein m is 1.

7. A nucleic acid labeling compound according to claim 2 , wherein A is H; Y is OH; Z is OH; L is —NH(CH 2 ) 4 NH—; Q is 5-carboxyfluorescein; and M is —CO(CH 2 ) 5 NH, wherein m is 1.

8. A nucleic acid labeling compound according to claim 2 , wherein A is H 4 O 9 P 3 —; Y is OH; Z is OH; L is —NH(CH 2 ) 4 NH—; Q is 5-carboxyfluorescein; and M is —CO(CH 2 ) 5 NH, wherein m is 1.

9. A nucleic acid labeling compound comprising the formula:

wherein A is H or a functional group that permits the attachment of the nucleic acid labeling compound to a nucleic acid;

X is O, S, NR 1 or CHR 2 , wherein R 1 and R 2 are, independently, H, alkyl or aryl;

Y is H, N 3 , F, OR 9 , SR 9 or NHR 9 , wherein R 9 , is H, alkyl or aryl;

Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl;

L is functionalized alkyl, alkenyl alkyl or alkynyl alkyl;

Q is a detectable moiety; and

M is a connecting group, wherein m is an integer ranging from 0 to about 3.

10. A nucleic acid labeling compound according to claim 9 , wherein A is H or H 4 O 9 P 3 —; X is O; Y is H or OR 9 , wherein R 9 , is H, alkyl or aryl; Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl; L is —CH═CH(CH 2 ) n NH—, wherein n is an integer ranging, from about 1 to about 10; Q is biotin or carboxyfluorescein; and M is —CO(CH 2 ) 5 NH— or —CO(CH 2 ) 5 NHCO(CH 2 ) 5 NH—, wherein m is 1 or 0.

11. A nucleic acid labeling compound according to claim 10 , wherein Y is H or OH; Z is H or OH; L is —CH═CHCH 2 NH—; Q is biotin; and m is 0.

12. A nucleic acid labeling compound according to claim 10 , wherein Y is H or OH; Z is H or OH; L is —CH═CHCH 2 NH—; Q is 5-carboxyfluorescein; and m is 0.

13. A nucleic acid labeling compound comprising the formula:

wherein A is H or a functional group that permits the attachment of the nucleic acid labeling compound to a nucleic acid;

X is O, S, NR 1 , or CHR 2 , wherein R 1 and R 2 are, independently, H, alkyl or aryl;

Y is H, N 3 , F, OR 9 , SR 9 or NHR 9 , wherein R 9 is H, alkyl or aryl;

Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl;

L is functionalized alkyl, alkenyl alkyl or alkynyl alkyl;

Q is a detectable moiety; and

M is a connecting group, wherein m is an integer ranging from 0 to about 3.

14. A nucleic acid labeling compound according to claim 13 , wherein A is H or H 4 O 9 P 3 —; X is O; Y is H or OR 9 , wherein R 9 is H, alkyl or aryl; Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl; L is —CH═CH(CH 2 ) n NH—, wherein n is an integer ranging from about 1 to about 10; Q is biotin or carboxyfluorescein; and M is —CO(CH 2 ) 5 NH— or —CO(CH 2 ) 5 NHCO(CH 2 ) 5 NH—, wherein m is 1 or 0.

15. A nucleic acid labeling compound according to claim 14 , wherein Y is H or OH; Z is H or OH; L is —CH═CHCH 2 NH—; Q is biotin; and m is 0.

16. A nucleic acid labeling compound according to claim 14 , wherein Y is H or OH; Z is H or OH; L is —CH═CHCH 2 NH—; Q is 5-carboxyfluorescein; and m is 0.

17. A nucleic acid labeling compound according to claim 1 , wherein the compound has the formula:

wherein A is H or a functional group that permits the attachment of the nucleic acid labeling compound to a nucleic acid;

X is O, S, NR 1 , or CHR 2 , wherein R 1 and R 2 are, independently, H, alkyl or aryl;

Y is H, N 3 , F, OR 9 , SR 9 or NHR 9 , wherein R 9 is H, alkyl or aryl;

Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl;

L is amino alkyl;

Q is a detectable moiety; and

M is a connecting group, wherein m is an integer ranging from 0 to about 3.

18. A nucleic acid labeling compound according to claim 9 , wherein the compound has the formula:

wherein A is H or a functional group that permits the attachment of the nucleic acid labeling compound to a nucleic acid;

X is O, S, NR 1 or CHR 2 , wherein R 1 and R 2 are, independently, H, alkyl or aryl;

Y is H, N 3 , F, OR 9 , SR 9 or NHR 9 , wherein R 9 is H, alkyl or aryl;

Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl;

L is functionalized alkyl, alkenyl alkyl or alkynyl alkyl;

Q is a detectable moiety; and

M is a connecting group, wherein m is an integer ranging from 0 to about 3.

19. A nucleic acid labeling compound according to claim 13 , wherein the compound has the formula:

wherein A is H or a functional group that permits the attachment of the nucleic acid labeling compound to a nucleic acid;

X is O, S, NR 1 or CHR 2 , wherein R 1 and R 2 are, independently, H, alkyl or aryl;

Y is H, N 3 , F, OR 9 , SR 9 , or NHR 9 , wherein R 9 is H, alkyl or aryl;

Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl;

L is functionalized alkyl, alkenyl alkyl or alkynyl alkyl;

Q is a detectable moiety; and

M is a connecting group, wherein m is an integer ranging from 0 to about 3.

20. A nucleic acid labeling compound according to claim 1 , wherein the compound has the formula:

wherein A is H or a functional group that permits the attachment of the nucleic acid labeling compound to a nucleic acid;

X is O, S, NR 1 or CHR 2 , wherein R 1 and R 2 are, independently, H, alkyl or aryl;

Y is H, N 3 , F, OR 9 , SR 9 or NHR 9 , wherein R 9 is H, alkyl or aryl;

Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl;

L is amino alkyl;

Q is a detectable moiety; and

M is a connecting group, wherein m is an integer ranging from 0 to about 3.

21. A nucleic acid labeling compound according to claim 9 , wherein the compound has the formula:

wherein A is H or a functional group that permits the attachment of the nucleic acid labeling compound to a nucleic acid;

X is O, S, NR 1 or CHR 2 , wherein R 1 and R 2 are, independently, H, alkyl or aryl;

Y is H, N 3 , F, OR 9 , SR 9 or NHR 9 , wherein R 9 is H, alkyl or aryl;

Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl;

L is functionalized alkyl, alkenyl alkyl or alkynyl alkyl;

Q is a detectable moiety; and

M is a connecting group, wherein m is an integer ranging from 0 to about 3.

22. A nucleic acid labeling compound according to claim 13 , wherein the compound has the formula:

wherein A is H or a functional group that permits the attachment of the nucleic acid labeling compound to a nucleic acid;

X is O, S, NR 1 or CHR 2 , wherein R 1 and R 2 are, independently, H, alkyl or aryl;

Y is H, N 3 , F, OR 9 , SR 9 or NHR 9 , wherein R 9 is H, alkyl or aryl;

Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl;

L is functionalized alkyl, alkenyl alkyl or alkynyl alkyl;

Q is a detectable moiety; and

M is a connecting group, wherein m is an integer ranging from 0 to about 3.

23. A nucleic acid labeling compound according to claim 1 , wherein the compound has the formula:

wherein A is H or a functional group that permits the attachment of the nucleic acid labeling compound to a nucleic acid;

X is O, S, NR 1 , or CHR 2 , wherein R 1 and R 2 are, independently, H, alkyl or aryl;

Y is H, N 3 , F, OR 9 , SR 9 or NHR 9 , wherein R 9 is H, alkyl or aryl;

Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl;

L is amino alkyl;

Q is a detectable moiety; and

M is a connecting group, wherein m is an integer ranging from 0 to about 3.

24. A nucleic acid labeling compound according to claim 9 , wherein the compound has the formula:

wherein A is H or a functional group that permits the attachment of the nucleic acid labeling compound to a nucleic acid;

X is O, S, NR 1 or CHR 2 , wherein R 1 and R 2 are, independently, H, alkyl or aryl;

Y is H, N 3 , F, OR 9 , SR 9 or NHR 9 , wherein R 9 is H, alkyl or aryl;

Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl;

L is functionalized alkyl, alkenyl alkyl or alkynyl alkyl;

Q is a detectable moiety; and

M is a connecting group, wherein m is an integer ranging from 0 to about 3.

25. A nucleic acid labeling compound according to claim 13 , wherein the compound has the formula:

wherein A is H or a functional group that permits the attachment of the nucleic acid labeling compound to a nucleic acid;

X is O, S, NR 1 or CHR 2 , wherein R 1 and R 2 are, independently, H, alkyl or aryl;

Y is H, N 3 , F, OR 9 , SR 9 , or NHR 9 , wherein R 9 is H, alkyl or aryl;

Z is H, N 3 , F or OR 10 , wherein R 10 is H, alkyl or aryl;

L is functionalized alkyl, alkenyl alkyl or alkynyl alkyl;

Q is a detectable moiety; and

M is a connecting group, wherein m is an integer ranging from 0 to about 3.

Assignments (4)
NOTICE OF RELEASE Recorded Apr 5, 2016
From: BANK OF AMERICA, N.A.
To: AFFYMETRIX, INC.
Reel/Frame 038361/0891 →
RELEASE OF SECURITY INTEREST Recorded Nov 13, 2015
From: GENERAL ELECTRIC CAPITAL CORPORATION, AS AGENT
To: AFFYMETRIX, INC.
Reel/Frame 037109/0132 →
SECURITY INTEREST Recorded Oct 28, 2015
From: AFFYMETRIX, INC.
To: BANK OF AMERICA, N.A., AS ADMINISTRATIVE AGENT
Reel/Frame 036988/0166 →
SECURITY AGREEMENT Recorded Jun 27, 2012
From: AFFYMETRIX, INC.
To: GENERAL ELECTRIC CAPITAL CORPORATION, AS AGENT
Reel/Frame 028465/0541 →