Nucleotide analogues
AssigneeQiagen Sciences, LLC
InventorsMong Sano Marma, Jerzy Olejnik, Ilia Korboukh
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Abstract
The present invention provides methods, compositions, mixtures and kits utilizing deoxynucleoside triphosphates comprising a 3′-O position capped by a group comprising methylenedisulfide as a cleavable protecting group and a detectable label reversibly connected to the nucleobase of said deoxynucleoside. Such compounds provide new possibilities for future sequencing technologies, including but not limited to Sequencing by Synthesis.
Claims10
A deoxynucleoside triphosphate having the structure:
- wherein D is a cleavable protecting group selected from the group consisting of an disulfide alkyl, disulfide substituted alkyl groups, disulfide allyl, and disulfide substituted allyl groups;
- B is a nucleobase;
- A is an attachment group selected from the group consisting of exocyclic amine, propargyl amine, and propargyl hydroxyl;
- C is a cleavable site core selected from the group consisting of:
- wherein R1 and R2 are independently selected alkyl groups;
- L1 and L2 are connecting groups;
- and Label is a detectable label selected from the group consisting of fluorophore dyes, energy transfer dyes, mass-tags, biotin, and haptenes.
A labeled deoxynucleoside triphosphate according to the following structure:
- wherein D is a cleavable protecting group selected from the group consisting of an disulfide alkyl, disulfide substituted alkyl groups, disulfide allyl, and disulfide substituted allyl groups;
- B is a nucleobase, A is an attachment group selected from the group consisting of propargyl, exocyclic amine, propargyl amine, and propargyl hydroxyl;
- C is a cleavable site core selected from the group consisting of:
- wherein R1 and R2 are independently selected alkyl groups;
- and L1 and L2 are connecting groups, wherein L1 is selected from the group consisting of —CONH(CH2)x—, —CO—O(CH2)x—, —CONH—(OCH2CH2O)x—, —CO—O(CH2CH2O)x—, and —CO(CH2)x—, wherein x is 0-10;
- and wherein L2 is selected from the group consisting of —CO—, —CONH—, —NHCONH—, —O—, —S—, —C═N, and —N═N—, alkyl, aryl, branched alkyl, branched aryl and combinations thereof and, wherein the label is a detectable label selected from the group consisting of fluorophore dyes, energy transfer dyes, mass-tags, biotin, and haptenes.
A deoxynucleoside triphosphate having the structure:
- wherein D is a cleavable protecting group selected from the group consisting of an disulfide alkyl, disulfide substituted alkyl groups, disulfide allyl, and disulfide substituted allyl groups;
- B is a nucleobase;
- Linker comprises a cleavable oxymethylenedisulfide-containing site core, wherein said cleavable site core is selected from the group consisting of:
- wherein R1 and R2 are independently selected alkyl groups;
- and Label is a detectable label selected from the group consisting of fluorophore dyes, energy transfer dyes, mass-tags, biotin, and haptenes.
Dependencies are inferred from the claim text.