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 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 a linker moeity;
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 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 amido alkyl; Q is biotin or a fluorescein; wherein m is 0, 1, or2.
3. A nucleic acid labeling compound according to claim 1 , wherein A is 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 —C(O)NH(CH 2 ) n NH—, wherein n is an integer ranging from about 2 to about 10; Q is biotin or a fluorescein; wherein m is 0, 1, or 2.
4. A nucleic acid labeling compound according to claim 1 , wherein Y is H or OH; Z is H or OH; L is —C(O)NH(CH 2 ) 4 NH—; and Q is biotin or a carboxyfluorescein.
5. A nucleic acid labeling compound according to claim 1 , wherein Y is OH; Z is H; L is —C(O)NH(CH 2 ) 4 NH—; m is 0; Q is biotin.
6. A nucleic acid labeling compound according to claim 1 , wherein Y is OH; Z is H; L is —C(O)NH(CH 2 ) 4 NH—; m is 0; and Q is a carboxyfluorescein.
7. A nucleic acid labeling compound according to claim 1 , having the structure:
8. A nucleic acid labeling compound according to claim 1 , having the structure:
9. A nucleic acid labeling compound according to claim 3 , wherein Y is H or OH; Z is H or OH; L is —C(O)NH(CH 2 ) 2 NH—; and Q is biotin or a carboxyfluorescein.
10. A nucleic acid labeling compound according to claim 9 , wherein Y is OH; Z is H; L is —C(O)NH(CH 2 ) 2 NH—; and Q is biotin.
11. A nucleic acid labeling compound according to claim 9 , wherein Y is OH; Z is H; and M is —C(O)(CH 2 ) 5 NH—.
12. A nucleic acid derivative produced by coupling a nucleic acid labeling compound according to claim 4 with a nucleic acid.
13. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 3 to a nucleic acid.