Nucleic acid labeling compounds
View Patent ↗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.
1. A nucleic acid labeling compound of the following structure:
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 10 , wherein R 10 is H, alkyl or aryl;
L is amido alkyl; Q is a detectable moiety; and
M is a connecting group, wherein m is an integer ranging from 0 to about 3.
2. The nucleic acid labeling compound according to claim 1 , wherein A is H or H 4 O 9 P 3 —; Y is H or OR 9 , wherein H 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 —C(O)NH(CH 2 ) n NH—, wherein n is an integer ranging from about 2 to about 10; Q is biotin or a carboxyfluorescein; and M is —CO(CH 2 ) 5 NH—, wherein m is 1 or 0.
3. The nucleic acid labeling compound according to claim 2 , wherein Y is H or OH; Z is H or OH; L is —C(O)NH(CH 2 ) 4 NH—; Q is biotin; M is —CO(CH 2 ) 5 NH—; and m is 1.
4. The nucleic acid labeling compound according to claim 2 , wherein Y is H or OH; Z is H or OH; L is —C(O)NH(CH 2 ) 4 NH—; Q is 5-carboxyfluorescein; and m is 0.
5. The nucleic acid labeling compound according to claim 2 , wherein A is H; Y is H; Z is H; L is —C(O)NH(CH 2 ) 4 NH—; Q is biotin; M is —CO(CH 2 ) 5 NH—; and m is 1.
6. The nucleic acid labeling compound according to claim 2 , wherein A is H 4 O 9 P 3 —; Y is H; Z is H; L is —C(O)NH(CH 2 ) 4 NH—; Q is biotin; M is —CO(CH 2 ) 5 NH—; and m is 1.
7. The nucleic acid labeling compound according to claim 2 , wherein A is H or OH; Z is H or OH; L is —C(O)NH(CH 2 ) 4 NH—; Q is 5-carboxyfluorescein; and m is 0.
8. The nucleic acid labeling compound according to claim 1 , wherein A is H 4 O 9 P 3 —; Y is H; Z is H; L is —C(O)NH(CH 2 ) 4 NH—; Q is 5-carboxyfluorescein; and m is 0.
9. The nucleic acid labeling compound according to claim 6 having the formula:
10. The nucleic acid labeling compound according to claim 6 having the formula:
11. The nucleic acid labeling compound according to claim 6 having the formula:
12. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 2 to a nucleic acid.
13. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 9 to a nucleic acid.
14. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 10 to a nucleic acid.
15. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 11 to a nucleic acid.
16. The nucleic acid labeling compound according to claim 8 having the formula:
17. The nucleic acid labeling compound according to claim 8 having the formula:
18. The nucleic acid labeling compound according to claim 8 having the formula:
19. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 16 to a nucleic acid.
20. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 17 to a nucleic acid.
21. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 18 to a nucleic acid.