Reagents utilizing a serinol scaffold for labeling synthetic oligonucleotides
AssigneesGlen Research Corporation, Nelson Biotechnologies, Inc.
InventorsPaul S. Nelson, Hugh Mackie, Andrew Murphy
Life of this patent
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Abstract
Novel CE-phosphoramidites and CPG reagents have been synthesized from a serinol backbone. These reagents are useful to introduce functional groups or directly label oligonucleotides. The versatile serinol scaffold allows for labeling at any position (5′ or 3′ termini, or any internal position) during automated DNA synthesis. Multiple labels or functional groups can be achieved by repetitive coupling cycles. Optimal spacer arms and protected label moieties have been specially designed. Further, the natural 3-carbon atom internucleotide phosphate distance is retained when inserted internally.
Claims24
A reagent having the following structure:
- wherein:
- R1=dimethoxytrityl (DMT), monomethoxytrityl (MMT), or other hydroxyl protecting group stable to oligonucleotide synthesis conditions;
- R2=phosphoramidityl
- wherein R3 and R4 are independently selected from the group consisting of C1-10 branched alkyl, C1-12 alkyl, and cyclic hydrocarbyls;
- and R5 is a phosphite-protecting group
- X1=—CO—CH2CH2 or —CO—CH2,
- X2=—NH—, —S—, or —O—;
- R6=a reporter substituent moiety selected from the group consisting of biotinyl, carboxyfluoresceinyl, propargyl, and a hapten-derived substituent moiety;
- or a suitable protecting group for X2.
A reagent having the following structure:
- wherein:
- R1=dimethoxytrityl (DMT), monomethoxytrityl (MMT), or other hydroxyl protecting group stable to oligonucleotide synthesis conditions;
- R2 is a long chain alkyl amine controlled pore glass attached through a succinyl linkage (-succinyl-CPG);
- X1=—CO—CH2CH2 or —CO—CH2;
- X2=—NH—, —S—, or —O—;
- R6=a reporter substituent moiety selected from the group consisting of biotinyl, carboxyfluoresceinyl, propargyl, and a hapten-derived substituent moiety;
- or a suitable protecting group for X2.
Dependencies are inferred from the claim text.