Click-Labeled Nucleosides and Phosphoramidites
AssigneeSomaLogic Operating Co., Inc.
InventorsCatherine R. Fowler, Brian E. Ream, John C. Rohloff
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Abstract
Click-labeled uridine bases, nucleosides, and phosphoramidites are provided, including improved methods of synthesis, oligonucleotides comprising the click-labeled nucleosides, methods of synthesizing spin-labeled oligonucleotides using click-labeled nucleotides, and spin-labeled oligonucleotides comprising click-labeled nucleosides.
Claims16
A method of producing the compound:
- or a salt thereof,
- wherein:
- X1 and X2 are each independently selected from methoxy and hydrogen;
- X3 is selected from methoxy, fluoro, hydrogen, and tert-butyldimethylsilyloxy;
- and
- Y is
- the method comprising reacting the compound
- or a salt thereof, with 2-cyanoethyl N,N,N′,N′-tetraisopropylphosphorodiamidite and pyridine trifluoroacetic acid in dichloromethane;
- or 2-cyanoethyl N,N-diisopropyl chlorophosphoramidite and diisopropylethylamine in dichloromethane.
A compound of Formula (I):
- or a salt thereof,
- wherein:
- X1 and X2 are each independently selected from methoxy and hydrogen;
- X3 is selected from methoxy, fluoro, hydrogen, and tert-butyldimethylsilyloxy;
- and
- Y is
A compound of Formula (II):
- or a salt thereof,
- wherein:
- X1 and X2 are each independently selected from methoxy and hydrogen;
- X3 is selected from methoxy, fluoro, hydrogen, and tert-butyldimethylsilyloxy;
- and
- Y is
An oligonucleotide comprising at least one click-labeled nucleotide, wherein at least one click-labeled nucleotide in the oligonucleotide has the structure:
- wherein:
- X3 is selected from a methoxy, fluoro, hydrogen, and tert-butyldimethylsilyloxy;
- X4 is selected from OH, —OR, —SR, and —Z—P(Z′)(Z″)O—R, wherein Z, Z′, and Z″ are each independently selected from O and S, and R is an adjacent nucleotide in the oligonucleotide;
- X5 is selected from —O-ss, —OR, —SR, and —Z—P(Z′)(Z″)O-T, wherein ss is a solid support, Z, Z′, and Z″ are each independently selected from O and S, and T is an adjacent nucleotide in the oligonucleotide;
- and
- Y is
An oligonucleotide comprising at least one 5-position modified nucleotide, wherein at least one modified nucleotide in the oligonucleotide has the structure:
- wherein:
- X3 is selected from a methoxy, fluoro, hydrogen, and tert-butyldimethylsilyloxy;
- X4 is selected from OH, —OR′, —SR′, and —Z—P(Z′)(Z″)O—R″, wherein Z, Z′, and Z″ are each independently selected from O and S, R′ is H or a cap, and R″ is H, a cap, or an adjacent nucleotide;
- X5 is selected from —O-ss, —OR′, —SR′, and —Z—P(Z′)(Z″)O—R″, wherein ss is a solid support, Z, Z′, and Z″ are each independently selected from O and S, R′ is H or a cap, and R″ is H, a cap, or an adjacent nucleotide;
- and
- W is a payload moiety.
An oligonucleotide comprising at least one 5-position modified nucleotide, wherein at least one modified nucleotide in the oligonucleotide has the structure:
- wherein:
- X3 is selected from a methoxy, fluoro, hydrogen, and tert-butyldimethylsilyloxy;
- X4 is selected from OH, —OR′, —SR′, and —Z—P(Z′)(Z″)O—R″, wherein Z, Z′, and Z″ are each independently selected from O and S, R′ is H or a cap, and R″ is H, a cap, or an adjacent nucleotide;
- X5 is selected from —O-ss, —OR′, —SR′, and —Z—P(Z′)(Z″)O—R″, wherein ss is a solid support, Z, Z′, and Z″ are each independently selected from O and S, R′ is H or a cap, and R″ is H, a cap, or an adjacent nucleotide;
- and
- W is a payload moiety.
A method of producing an oligonucleotide comprising at least one 5-position modified nucleoside, comprising synthesizing an oligonucleotide comprising at least one nucleotide having the structure:
- wherein:
- X3 is selected from a methoxy, fluoro, hydrogen, and tert-butyldimethylsilyloxy;
- X4 is selected from OH, —OR, —SR, and —Z—P(Z′)(Z″)O—R, wherein Z, Z′, and Z″ are each independently selected from O and S, and R is selected from H, a 5′ cap, and an adjacent nucleotide;
- X5 is selected from —O-ss, —OR, —SR, and —Z—P(Z′)(Z″)O—R, wherein ss is a solid support, Z, Z′, and Z″ are each independently selected from O and S, and R is selected from H and an adjacent nucleotide;
- and
- Y is
- and reacting the oligonucleotide with a reagent comprising a payload moiety and an azide moiety.
A method of producing an oligonucleotide comprising at least one 5-position modified nucleoside, comprising synthesizing an oligonucleotide comprising at least one nucleotide having the structure:
- wherein:
- X3 is selected from a methoxy, fluoro, hydrogen, and tert-butyldimethylsilyloxy;
- X4 is selected from OH, —OR, —SR, and —Z—P(Z′)(Z″)O—R, wherein Z, Z′, and Z″ are each independently selected from O and S, and R is selected from H, a 5′ cap, and an adjacent nucleotide;
- X5 is selected from —O-ss, —OR, —SR, and —Z—P(Z′)(Z″)O—R, wherein ss is a solid support, Z, Z′, and Z″ are each independently selected from O and S, and R is selected from H and an adjacent nucleotide;
- and
- Y is
- and reacting the oligonucleotide with a reagent comprising a payload moiety and a tetrazine moiety.
Dependencies are inferred from the claim text.