Methods, kits and compositions pertaining to combination oligomers and libraries for their preparation
First Claim
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1. An array of at least two oligomers, wherein at least one of the oligomers is a combination oligomer that comprises a segment having the formula:
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A-B-Cwherein;
each of A and C is an oligomer block independently selected from the group consisting of a peptide nucleic acid, a PNA chimera and a PNA combination oligomer and each of A and C is optionally linked to other moieties; and
B is a linker of at least three atoms in length that covalently links oligomer block A to oligomer block C;
wherein;
oligomer blocks A and C taken together encode a probing nucleobase sequence that is designed to sequence specifically hybridize juxtaposed to a target sequence of contiguous nucleobases, such that there is no gap or gap base, to thereby form a double stranded target sequence/combination oligomer complex.
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Abstract
This invention pertains to the field of combination oligomers, including the block synthesis of combination oligomers in the absence of a template, as well as related methods, kits, libraries and other compositions.
49 Citations
27 Claims
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1. An array of at least two oligomers, wherein at least one of the oligomers is a combination oligomer that comprises a segment having the formula:
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A-B-Cwherein; each of A and C is an oligomer block independently selected from the group consisting of a peptide nucleic acid, a PNA chimera and a PNA combination oligomer and each of A and C is optionally linked to other moieties; and B is a linker of at least three atoms in length that covalently links oligomer block A to oligomer block C; wherein; oligomer blocks A and C taken together encode a probing nucleobase sequence that is designed to sequence specifically hybridize juxtaposed to a target sequence of contiguous nucleobases, such that there is no gap or gap base, to thereby form a double stranded target sequence/combination oligomer complex. - View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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2. The away of clam 1, wherein the linker is not part of a nucleobase containing backbone subunit of the polymer.
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14. A method comprising:
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(a) reacting, at a site on a solid surface, a first oligomer block, a second oligomer block, and optionally a condensation reagent or reagents under condensation conditions to thereby form a combination oligomer having a linker of at least three atoms in length that covalently links the first oligomer block to the second oligomer block; wherein; (i) one of said two oligomer blocks is support bound; (ii) each of the first and second oligomer blocks independently selected from the group consisting of a peptide nucleic acid, a PNA chimera and a PNA combination oligomer; (iii) one or both oligomer blocks do not comprise nucleobase protecting groups; and (iv) the combination oligomer forms in the absence of a template; and (b) repeating step (a) at one or more sites until the array of combination oligomers is constructed, with the further proviso that the first and second oligomer blocks taken together encode a probing nucleobase sequence that is designed to sequence specifically hybridize juxtaposed to a target sequence of contiguous nucleobases, such that there is no gap or gap base, to thereby form a double stranded target sequence/combination oligomer complex. - View Dependent Claims (15)
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16. A method comprising:
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(a) reacting, at a site on a solid surface, a combination oligomer having a linker of at least three atoms in length that covalently links the first oligomer block to the second oligomer block with a surface functional group to thereby attached the combination oligomer to the surface of the array, wherein; (i) each of the first and second oligomer blocks independently selected from the group consisting of a peptide nucleic acid, a PNA chimera and a PNA combination oligomer; (ii) one or both oligomer blocks do not comprise nucleobase protecting groups; and (b) repeating step (a) at one or more sites until the array of combination oligomers is constructed, with the further proviso that the combination oligomer hybridizes juxtaposed to a target sequence of contiguous nucleobases, with no gap or gap base. - View Dependent Claims (17)
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18. An array of at least two oligomers, wherein at least one of the oligomers is a combination oligomer that comprises a segment having the formula:
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A-B-Cwherein; each of A and C is an oligomer block independently selected from the group consisting of a peptide nucleic acid, a PNA chimera and a PNA combination oligomer and each of A and C is optionally linked to other moieties; and B is a linker of at least three atoms in length that covalently links oligomer block A to oligomer block C; wherein; oligomer blocks A and C taken together encode a probing nucleobase sequence that is designed to sequence specifically hybridize juxtaposed to a target sequence of contiguous nucleobases, such that there is no gap or gap base, to thereby form a double stranded target sequence/combination oligomer complex, with the further proviso that the linker is not part of a nucleobase containing backbone subunit of the polymer.
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19. An array of at least two oligomers, wherein at least one of the oligomers is a combination oligomer that comprises a segment having the formula:
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A-B-Cwherein; each of A and C is an oligomer block independently selected from the group consisting of a peptide nucleic acid, a PNA chimera and a PNA combination oligomer and each of A and C is optionally linked to other moieties; and B is a linker of at least three atoms in length that covalently links oligomer block A to oligomer block C; wherein; oligomer blocks A and C taken together encode a probing nucleobase sequence that is designed to sequence specifically hybridize juxtaposed to a target sequence of contiguous nucleobases, such that there is no gap or gap base, to thereby form a double stranded target sequence/combination oligomer complex, and wherein at least one of the at least two oligomers further comprises at least one energy transfer set of labels such that at least one acceptor moiety of the energy transfer set is linked to one of the linked oligomer blocks of the combination oligomer whilst at least one donor moiety of the energy transfer set is linked to another of the linked oligomer blocks of the combination oligomer, wherein the labels of the set are linked to the oligomer blocks at positions that facilitate a change in detectable signal of at least one label when the combination oligomer is hybridized to the target sequence as compared to when the combination oligomer is in a non-hybridized state. - View Dependent Claims (20, 21, 22, 23)
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24. A method comprising:
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(a) reacting, at a site on a solid surface, a first oligomer block, a second oligomer block, and optionally a condensation reagent or reagents under condensation conditions to thereby form a combination oligomer having a linker of at least three atoms in length that covalently links the first oligomer block to the second oligomer block, wherein; (i) one of said two oligomer blocks is support bound; (ii) each of the first and second oligomer blocks independently selected from the group consisting of a peptide nucleic acid, a PNA chimera and a PNA combination oligomer; (iii) one or both oligomer blocks do not comprise nucleobase protecting groups; and (iv) the combination oligomer forms in the absence of a template; and (b) repeating step (a) at one or more sites until the array of combination oligomers is constructed, with the further proviso that the linker is not part of a nucleobase containing backbone subunit of the polymer. - View Dependent Claims (25)
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26. A method comprising:
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(a) reacting, at a site on a solid surface, a combination oligomer having a linker of at least three atoms in length that covalently links the first oligomer block to the second oligomer block with a surface functional group to thereby attached the combination oligomer to the surface of the array, wherein; (i) each of the first and second oligomer blocks independently selected from the group consisting of a peptide nucleic acid, a PNA chimera and a PNA combination oligomer; (ii) one or both oligomer blocks do not comprise nucleobase protecting groups; and (b) repeating step (a) at one or more sites until the array of combination oligomers is constructed, with the further proviso that the linker is not part of a nucleobase containing backbone subunit of the polymer. - View Dependent Claims (27)
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Specification