Nucleotide analogues
Disclosed herein, interalia, are compounds, compositions, and methods of using the same for the sequencing of a nucleic acid.
1. A nucleic acid molecule comprising a nucleotide, wherein said nucleotide comprises (i) a cleavable moiety covalently bound to the 3′ oxygen of said nucleotide, said cleavable moiety having the formula -L 1P -S—S—R 6P (I); wherein,
L 1P is a substituted methylene, wherein L 1P is substituted with a substituted or unsubstituted alkyl, or a substituted or unsubstituted heteroalkyl;
R 6P is unsubstituted C 1 -C 4 alkyl; and
(ii) a detectable moiety attached to said nucleotide via a covalent linker, wherein said covalent linker comprises
wherein,
R 102 is unsubstituted C1-C4 alkyl.
2. The nucleic acid molecule of claim 1 , wherein R 6P is unsubstituted methyl or unsubstituted ethyl.
3. The nucleic acid molecule of claim 1 , wherein the nucleotide comprises a cytosine or a derivative thereof, guanine or a derivative thereof, adenine or a derivative thereof, thymine or a derivative thereof, uracil or a derivative thereof, hypoxanthine or a derivative thereof, xanthine or a derivative thereof, 7-methylguanine or a derivative thereof, 5,6-dihydrouracil or a derivative thereof, 5-methylcytosine or a derivative thereof, or 5-hydroxymethylcytosine or a derivative thereof.
4. The nucleic acid molecule of claim 1 , wherein said nucleotide is an adenine nucleotide, a cytosine nucleotide, a thymidine nucleotide, or a guanosine nucleotide.
5. The nucleic acid molecule of claim 1 , wherein L 1P is substituted with unsubstituted alkyl or unsubstituted heteroalkyl.
6. The nucleic acid molecule of claim 1 , wherein L 1P is substituted with unsubstituted alkyl.
7. The nucleic acid molecule of claim 1 , wherein L 1P is
8. The nucleic acid molecule of claim 1 , wherein L 1P is
9. The nucleic acid molecule of claim 1 , wherein -L 1P -S—S-R 6P is:
10. The nucleic acid molecule of claim 1 , wherein -L 1P -S—S-R 6P is:
11. The nucleic acid molecule of claim 1 , wherein -L 1P -S—S-R 6P is:
12. The nucleic acid molecule of claim 1 , wherein said 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 nucleic acid molecule of claim 1 , wherein said detectable moiety is a xanthene derivative or cyanine derivative.
14. The nucleic acid molecule of claim 1 , wherein said nucleic acid molecule is in a cell.
15. The nucleic acid molecule of claim 1 , wherein said nucleic acid molecule is bound to a template polynucleotide.
16. The nucleic acid molecule of claim 1 , wherein said nucleotide is
wherein
L 100 is said covalent linker, is the attachment point to the remainder of the nucleic acid molecule, and R 4 is said detectable moiety.
17. The nucleic acid molecule of claim 1 , wherein L 1P is
18. The nucleic acid molecule of claim 1 , wherein the covalent linker comprises
wherein R 102 is unsubstituted C 1 -C 4 alkyl.
19. The nucleic acid molecule of claim 1 , wherein the covalent linker comprises
wherein R 102 is unsubstituted C 1 -C 4 alkyl.
20. The nucleic acid molecule of claim 1 , wherein R 102 is unsubstituted methyl or unsubstituted ethyl.
21. The nucleic acid molecule of claim 1 , wherein R 102 is unsubstituted propyl.