Nucleotide analogues
Disclosed herein, interalia, are compounds, compositions, and methods of using the same for the sequencing of a nucleic acid.
1. A kit comprising a labeled nucleotide, wherein the labeled nucleotide comprises:
(i) a cleavable moiety covalently bound to the 3′ oxygen of said labeled nucleotide, wherein the cleavable moiety has the formula -L 1P -S—S—R 6P (I); and
(ii) a nucleobase linked via a covalent linker to a first detectable moiety, wherein said covalent linker comprises
wherein,
R 102 is unsubstituted C 1 -C 4 alkyl;
L 1P is a substituted methylene, wherein L 1P is substituted with a substituted or unsubstituted alkyl, or a substituted or unsubstituted heteroalkyl; and
R 6P is unsubstituted methyl or unsubstituted ethyl.
2. The kit of claim 1 , wherein the labeled nucleotide comprises a divalent cytosine or a derivative thereof, divalent guanine or a derivative thereof, divalent adenine or a derivative thereof, divalent thymine or a derivative thereof, divalent uracil or a derivative thereof, divalent hypoxanthine or a derivative thereof, divalent xanthine or a derivative thereof, divalent 7-methylguanine or a derivative thereof, divalent 5,6-dihydrouracil or a derivative thereof, divalent 5-methylcytosine or a derivative thereof, or divalent 5-hydroxymethylcytosine or a derivative thereof.
3. The kit of claim 1 , wherein the labeled nucleotide is labeled adenine nucleotide, a labeled cytosine nucleotide, a labeled thymidine nucleotide, or a labeled guanosine nucleotide.
4. The kit of claim 1 , wherein the kit comprises
a labeled adenine nucleotide comprising the cleavable moiety of formula (I), wherein the labeled adenine nucleotide is linked via the covalent linker to the first detectable moiety,
a labeled cytosine nucleotide comprising the cleavable moiety of formula (I), wherein the labeled cytosine nucleotide is linked via the covalent linker to a second detectable moiety,
a labeled thymidine nucleotide comprising the cleavable moiety of formula (I), wherein the labeled thymidine nucleotide is linked via the covalent linker to a third detectable moiety, and
a labeled guanosine nucleotide comprising the cleavable moiety of formula (I), wherein the labeled guanosine nucleotide is linked via the covalent linker to a fourth detectable moiety
wherein the first detectable moiety, the second detectable moiety, the third detectable moiety, and the fourth detectable moiety are optionally different.
5. The kit of claim 4 , wherein L 1P is substituted with unsubstituted alkyl or unsubstituted heteroalkyl.
6. The kit of claim 4 , wherein L 1P is substituted with unsubstituted alkyl.
7. The kit of claim 1 , wherein L 1P is
8. The kit of claim 1 , wherein L 1P is
9. The kit of claim 1 , wherein L 1P -S—S—R 6P is:
10. The kit of claim 1 , wherein -L 1P -S—S—R 6P is:
11. The kit of claim 1 , wherein -L 1P -S—S—R 6P is:
12. The kit of claim 1 , wherein the first detectable moiety is a xanthene derivative, cyanine derivative, naphthalene derivative, coumarin derivative, oxadiazole derivative, anthracene derivative, pyrene derivative, oxazine derivative, acridine derivative, arylmethine derivative, or tetrapyrrole derivative.
13. The kit of claim 11 , wherein said first detectable moiety is a xanthene derivative, cyanine derivative, naphthalene derivative, coumarin derivative, oxadiazole derivative, anthracene derivative, pyrene derivative, oxazine derivative, acridine derivative, arylmethine derivative, or tetrapyrrole derivative.
14. The kit of claim 1 , wherein the detectable moiety is a xanthene derivative or cyanine derivative.
15. The kit of claim 4 , wherein the detectable moiety is a xanthene derivative or cyanine derivative.
16. The kit of claim 1 , further comprising a polymerase and a solid substrate.
17. The kit of claim 4 comprising
wherein
L 100 is said covalent linker and R 4 is independently said first detectable moiety, said second detectable moiety, third detectable moiety, or said fourth detectable moiety.
18. The kit of claim 1 , wherein the covalent linker comprises
wherein R 102 is unsubstituted C 1 -C 4 alkyl.
19. The kit of claim 1 , wherein L 1P
20. The kit of claim 1 , wherein the covalent linker comprises
wherein R 102 is unsubstituted C 1 -C 4 alkyl.
21. The kit of claim 20 , wherein R 102 is unsubstituted methyl, unsubstituted ethyl, or unsubstituted propyl.