Combinatorial nucleobase oligomers comprising universal base analogues and methods for making and using same
First Claim
1. An insulating nucleobase oligomer block library comprising a plurality of insulating nucleobase oligomer blocks, wherein each oligomer block independently comprises a sequence of polymerized nucleobases having termini, said sequence including at least three specificity-determining nucleobases and at least one universal nucleobase, and at least one chemically reactive moiety that is covalently coupled to a terminus of the polymerized nucleobase sequence, wherein a universal nucleobase comprises a base that does not significantly discriminate between bases on a complementary polymeric structure having nucleobases, and a specificity-determining nucleobase is capable of discriminating between bases on a complementary polymeric structure having nucleobases, the chemically reactive moiety on one oligomer block is capable of reacting with the chemically reactive moiety on at least one other oligomer block to form a covalent linker between the oligomer blocks in the absence of a template to form an insulating combinatorial nucleobase oligomer, and the insulating combinatorial nucleobase oligomer has a hybridization target sequence that is a composite of the specificity-determining nucleobases in the oligomer blocks comprising the insulating combinatorial nucleobase oligomer.
6 Assignments
0 Petitions
Accused Products
Abstract
The invention relates to insulating combinatorial nucleobase oligomers that comprise universal base analogs, where the oligomers are formed by the ligation of two or more oligomer “blocks” via a covalent linkage. Universal bases may serve to insulate specifically binding nucleobases from the effects of the covalent linker region joining two oligomer blocks together, so that the universal bases at least partially negate the Tm penalty caused by the covalent linkage, effective to reduce the required minimal length of the oligomer blocks and the combinatorial oligomer. The resulting insulating nucleobase combinatorial oligomers find use in any hybridization-based application, including use as probes and primers. The combinatorial oligomers of the present invention provide advantages over existing combinatorial oligomer systems currently known in the art.
22 Citations
76 Claims
-
1. An insulating nucleobase oligomer block library comprising a plurality of insulating nucleobase oligomer blocks, wherein
each oligomer block independently comprises a sequence of polymerized nucleobases having termini, said sequence including at least three specificity-determining nucleobases and at least one universal nucleobase, and at least one chemically reactive moiety that is covalently coupled to a terminus of the polymerized nucleobase sequence, wherein a universal nucleobase comprises a base that does not significantly discriminate between bases on a complementary polymeric structure having nucleobases, and a specificity-determining nucleobase is capable of discriminating between bases on a complementary polymeric structure having nucleobases, the chemically reactive moiety on one oligomer block is capable of reacting with the chemically reactive moiety on at least one other oligomer block to form a covalent linker between the oligomer blocks in the absence of a template to form an insulating combinatorial nucleobase oligomer, and the insulating combinatorial nucleobase oligomer has a hybridization target sequence that is a composite of the specificity-determining nucleobases in the oligomer blocks comprising the insulating combinatorial nucleobase oligomer.
-
26. An insulating combinatorial nucleobase oligomer, comprising a plurality of covalently linked insulating nucleobase oligomer blocks, said plurality of covalently linked insulating nucleobase oligomer blocks comprising at least a first insulating nucleobase oligomer block covalently linked to a second insulating nucleobase oligomer block by a covalent linker, wherein:
-
said first and said second insulating nucleobase oligomer blocks each comprise at least three specificity-determining nucleobases covalently linked to a polymeric backbone structure, and at least one universal nucleobase covalently linked to said backbone structure; and
said covalent linker comprises a chemical bond resulting from a chemical reaction between chemically reactive moieties of said first and said second insulating nucleobase oligomer blocks in the absence of a template. - View Dependent Claims (27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46)
-
-
47. A method for the synthesis of an insulating combinatorial nucleobase oligomer, comprising:
-
selecting two or more oligomer blocks from the oligomer block library of claim 0, where the chemically reactive moieties on the oligomer blocks are capable of reacting to form a covalent linker between the oligomer blocks in the absence of a template, and reacting the selected oligomer blocks under suitable conditions whereby the chemically reactive moieties on the oligomer blocks combine to form a covalent linker between the oligomer blocks, thereby forming the insulating combinatorial nucleobase oligomer. - View Dependent Claims (48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72)
-
-
73. An insulating nucleobase oligomer block construct, comprising:
-
A solid support; and
An insulating nucleobase oligomer block comprising a sequence of polymerized nucleobases having a terminus, said sequence including at least three specificity-determining nucleobases and at least one universal nucleobase, and at least one chemically reactive moiety that is covalently coupled to a terminus of the polymerized nucleobase sequence, Wherein the insulating combinatorial nucleobase oligomer has a hybridization target sequence that is a composite of the specificity-determining nucleobases in the oligomer blocks comprising the insulating combinatorial nucleobase oligomer, and the chemically reactive moiety is capable of reacting with a chemically reactive moiety on another oligomer block to form a covalent linker between the oligomer blocks in the absence of a template to form an insulating combinatorial nucleobase oligomer affixed to said solid support. - View Dependent Claims (74, 75, 76)
-
Specification