Back to results
US 11,230,734 B2Granted
Modified nucleotide linkers
AssigneeIllumina Cambridge Limited
InventorsXiaolin Wu, Xiaohai Liu
Life of this patent
Estimating the term…
Abstract
Some embodiments of the present application relate to novel modified nucleotide linkers for increasing the efficiency of nucleotide incorporation in Sequencing by Synthesis applications. Methods of preparing these modified nucleotide linkers are also provided herewith.
Claims23
A nucleoside or nucleotide covalently attached to a fluorophore through a linker, wherein said linker comprises a structure of formula (III):
- wherein
- L1 is absent, or comprises a structure of formula (I), (II), or combinations thereof;
- wherein
- R1 is hydrogen or C1-6 alkyl;
- R2 is hydrogen or C1-6 alkyl;
- R3 is C1-6 alkyl, —NR5—C(═O)R6, or —NR7—C(═O)—OR8;
- R4 is hydrogen or C1-6 alkyl;
- each of R5 and R7 is independently hydrogen, C1-6 alkyl, phenyl, or C7-12 aralkyl;
- each of R6 and R8 is independently C1-6 alkyl, phenyl, C7-12 aralkyl, or C3-7 cycloalkyl;
- X is methylene (CH2), oxygen (O), or sulfur (S);
- m is an integer of 0 through 20;
- n is an integer of 1 through 20;
- and
- p is an integer of 1 through 20;
- L2 is C1-10 alkylene, C3-6 heteroalkylene, C1-10 alkylene interrupted by a substituted phenyl group, or C3-6 heteroalkylene interrupted by a substituted phenyl group, wherein the C3-6 heteroalkylene comprising one or more nitrogen atoms and optionally substituted with oxo (═O), and wherein the substituted phenyl group is substituted with one to four substituents selected from the group consisting of nitro, cyano, halo, hydroxy, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy and sulfonyl hydroxide;
- L3 is C1-6 alkylene, or C2-6 heteroalkylene comprising one or more oxygen atoms;
- RA is hydrogen, cyano, hydroxy, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, or azido, and wherein at least one of the repeating units of
- comprises an azido group;
- Z is oxygen (O) or NRC;
- each of RB and RC is independently hydrogen or C1-6 alkyl;
- and
- k is an integer of 1 through 10.
19 more elements
A reagent for modifying a nucleoside or a nucleotide, comprising a fluorophore and a linker, said linker comprises a structure of formula (III):
- wherein
- L1 is absent, or comprises a structure of formula (I), (II), or combinations thereof;
- wherein
- R1 is hydrogen or C1-6 alkyl;
- R2 is hydrogen or C1-6 alkyl;
- R3 is C1-6 alkyl, —NR5—C(═O)R6, or —NR7—C(═O)—OR8;
- R4 is hydrogen or C1-6 alkyl;
- each of R5 and R7 is independently hydrogen, C1-6 alkyl, phenyl, or C7-12 aralkyl;
- each of R6 and R8 is independently C1-6 alkyl, phenyl, C7-12 aralkyl, or C3-7 cycloalkyl;
- X is methylene (CH2), oxygen (O), or sulfur (S);
- m is an integer of 0 through 20;
- n is an integer of 1 through 20;
- and
- p is an integer of 1 through 20;
- L2 is C1-10 alkylene, C3-6 heteroalkylene, C1-10 alkylene interrupted by a substituted phenyl group, or C3-6 heteroalkylene interrupted by a substituted phenyl group, wherein the C3-6 heteroalkylene comprising one or more nitrogen atoms and optionally substituted with oxo (═O), and wherein the substituted phenyl group is substituted with one to four substituents selected from the group consisting of nitro, cyano, halo, hydroxy, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy and sulfonyl hydroxide;
- L3 is C1-6 alkylene, or C2-6 heteroalkylene;
- RA is hydrogen, cyano, hydroxy, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, or azido, and wherein at least one of the repeating units of
- comprises an azido group;
- Z is oxygen (O) or NRC;
- each of RB and RC is independently hydrogen or C1-6 alkyl;
- and
- k is an integer of 1 through 10.
19 more elements
Dependencies are inferred from the claim text.