Abstract: Disclosed herein are embodiments of a solid support suitable for synthesizing nucleic acid sequences. The solid support may have a structure according to Formula I, where CPG is controlled pore glass, and m, n, x, y, R1 and R2 are as defined herein. Also disclosed are methods for making and using the solid support, kits including solid support, and a universal linker phosphoramidite suitable for use in the solid support.

Abstract: Disclosed herein are embodiments of a solid support suitable for synthesizing nucleic acid sequences. The solid support may have a structure according to Formula I, where CPG is controlled pore glass, and m, n, x, y, R1 and R2 are as defined herein. Also disclosed are methods for making and using the solid support, kits including solid support, and a universal linker phosphoramidite suitable for use in the solid support.

Abstract: The invention provides a compound of the formula: and a capture support of the formula: wherein R1, R2, R3, R6, A, B, D, E, J, K, Q, W, and Z are as defined herein. The invention also provides a method of purifying an oligonucleotide or an oligonucleotide analog composed of “b” nucleotides from a mixture comprising the oligonucleotide or oligonucleotide analog and at least one oligonucleotide or oligonucleotide analog composed of “a” nucleotides, wherein b?a, comprising use of the compound and the capture support.

Abstract: The invention provides a compound of the formula: and a capture support of the formula: wherein R1, R2, R3, R6, A, B, D, E, J, K, Q, W, and Z are as defined herein. The invention also provides a method of purifying an oligonucleotide or an oligonucleotide analog composed of “b” nucleotides from a mixture comprising the oligonucleotide or oligonucleotide analog and at least one oligonucleotide or oligonucleotide analog composed of “a” nucleotides, wherein b?a, comprising use of the compound and the capture support.

Abstract: Compounds of the formula (Z)x wherein: each Z is independently selected from 2?-deoxythymidinyl moiety, 2?-deoxyadenosinyl moiety, and a 2?-deoxycytidinyl moiety, x is an integer from 5-20, wherein said 2?-deoxythymidinyl moieties are connected by thiophosphate triester linkages, and 3-12 of said thiophosphate triester linkages being positively charged linkages of the formula: where n is an integer from 2 to 6; and the remainder of the thiophosphate triester linkages are neutral linkages of the formula: provided that when x is 5-6, the number of positively charged linkages is 3, when x is 7-8, the number of positively charged linkages is 3-4, when x is 9-12, the number of positively charged linkages is 3-10, and when x is 13-20, the number of positively charged linkages is 4-12.

Abstract: The present invention provides a CpG oligonucleotide prodrug that includes a thermolabile substituent on at least one nucleotide thereof. The present invention also provides compositions that include a carrier and a therapeutically effective amount of at least one CpG oligonucleotide prodrug. The present invention further provides therapeutic methods of using such thermolabile CpG oligonucleotide prodrugs and compositions thereof. The present invention further provides a method of inhibiting tetrad formation in a CpG oligonucleotide by functionalizing the CpG oligonucleotide with one or more thermolabile substituents.

Abstract: Disclosed are O-protected compounds of the formula (I): wherein B is an optionally protected nucleobase, and R1-R3 are as described herein, wherein at least one of R1-R3 is —CH2—O—N?CHR. The compounds are useful as intermediates in oligonucleotide synthesis. Also disclosed is a method of preparing the compounds from nucleosides via a process comprising conversion of a hydroxyl group to a methylthiomethoxy group, and a method of preparing oligonucleotides such as RNA starting from the compounds. The —CH2—O—N?CHR group is stable during oligonucleotide synthesis and can be easily removed after synthesis via, for example, treatment with a base.

Abstract: Disclosed are O-protected compounds of the formula (I): wherein B is an optionally protected nucleobase, and R1-R3 are as described herein, a method of preparing such compounds, and a method of preparing oligonucleotides such as RNA starting from such compounds. The O-protected compounds have one or more advantages, for example, the 2?-O-protected compound is stable during the various reaction steps involved in oligonucleotide synthesis; the protecting group can be easily removed after the synthesis of the oligonucleotide, for example, by reaction with tetrabutylammonium fluoride; and/or the O-protected groups do not generate DNA/RNA alkylating side products, which have been reported during removal of 2?-O-(2-cyanoethyl)oxymethyl or 2?-O-[2-(4-tolylsulfonyl)ethoxymethyl groups under similar conditions.

Abstract: Provided is a hydroxyl-protected alcohol comprising a thermolabile hydroxyl-protecting group comprising a 2-pyridyl substituent and a precursor of the thermolabile hydroxyl-protected alcohol. An exemplary thermolabile hydroxyl-protected alcohol is represented by the formula Pg-O—R, wherein Pg is a protecting group of the formula: (Formula) wherein: A is a 2-pyridyl; Z is CH2 or NR1; R1, R2, R2?, R3 and R3? are the same or different and each can be, e.g., H, alkyl, or alkyl comprising an aryl substituent; W is CO, CS, or SO; and R is the organic residue of the hydroxyl-protected alcohol. Also provided is a method of producing an alcohol, which method comprises heating the hydroxyl-protected alcohol, which optionally may be obtained from a precursor, at a temperature effective to cleave the hydroxyl-protecting group. The method can be used to produce oligonucleotides.

Abstract: The present invention provides a CpG oligonucleotide prodrug that includes a thermolabile substituent on at least one nucleotide thereof. The present invention also provides compositions that include a carrier and a therapeutically effective amount of at least one CpG oligonucleotide prodrug. The present invention further provides therapeutic methods of using such thermolabile CpG oligonucleotide prodrugs and compositions thereof. The present invention further provides a method of inhibiting tetrad formation in a CpG oligonucleotide by functionalizing the CpG oligonucleotide with one or more thermolabile substituents.

Abstract: Provided is a hydroxyl-protected alcohol of the formula R—O—Pg, wherein Pg is a protecting group of the formula: wherein Y, Z, W, R1, R1a, R2, R2a, R3, R3a, R4, R4a, a, b, c, d, e and f are defined herein and R is a nucleosidyl group, an oligonucleotidyl group with 2 to about 300 nucleosides, or an oligomer with 2 to about 300 nucleosides. Also provided is a deprotection method, which includes heating the hydroxyl-protected alcohol at a temperature effective to cleave thermally the hydroxyl-protecting group therefrom.

Abstract: The present invention provides a compound of formula (I), (II), or (III), wherein R1, R2, R2?, R3, and R3? are the same or different and each is H an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl, or an aralkyl. Alternatively, either of R2 or R2? combined with either of R3 or R3? comprises a ring. R4 is a protecting group or a solid support R5 is H or an alkyl. R6 is a protecting group, an amidoalkyl, an alkyl, an alkyl ketone, an alkenyl, an alkynyl, a cycloalkyl, an aryl, or an aralkyl. R15 is H or a protecting group. Q and Q1 are the same or different and each is a nucleoside, an oligonucleotide comprising a nucleoside, or an oligomer comprising a nucleoside, which is of formula (a) or (b), wherein B is a labeling group, an alkyl, an alkenyl, an alkynyl, a cyclic group optionally containing one or more heteroatoms, or an amino; and, E is H, a halogen, a hydroxy, an alkoxy, an ester, an amino or a protecting group. X and X1 are independently O, S, or Se, and n is an integer from 1 to about 300.

Abstract: The invention provides a method of thermally deprotecting the internucleosidic phosphorus linkage of an oligonucleotide, which method comprises heating a protected oligonucleotide in a fluid medium at a substantially neutral pH, so as to deprotect the oligonucleotide. The present invention further provides a method of synthesizing an oligonucleotide using the thermal deprotection method described above, and novel oligonucleotides and intermediates that incorporate the thermolabile protecting group used in accordance with the present invention.

Abstract: The invention provides a method of thermally deprotecting the internucleosidic phosphorus linkage of an oligonucleotide, which method comprises heating in a fluid medium at a substantially neutral pH.

Abstract: Method for substituting a substitution compound for the hydrogen of a support bound primary hydroxyl group. The support bound primary hydroxyl group is treated in an organic, substantially anhydrous solvent in the presence of a tertiary amine base and the substitution compound.The substitution compound has a positive moiety and a negative moiety. The positive moiety is selected from the group consisting of trityl, pixyl, and derivatives thereof.The reagent is selected from the group consisting of tetraalkylammonium salts, inorganic salts, and mixtures thereof. Each reagent has a cation and an anion moiety.The cation moiety of the reagent is more electropositive than the positive moiety of the substitution compound. This relationship enables the reagent to attract the negative moiety of the substitution compound.

Abstract: A method is disclosed for the sulfurization of a phosphorus containing compound, which comprises: solubilizing the phosphorous containing compound and then contacting the phosphorous containing compound, with a sulfur containing compound of the solution formula: ##STR1## wherein, B is selected from the group consisting of --CH.sub.2 --, --C(O)-- or --C(S)--;Q is a non-interfering moiety or radical; andm and n, same or different, are selected from the group consisting of zero or one.

Abstract: A new class of nucleoside phosphoramidites which are relatively stable to permit isolation thereof and storage at room temperature. The phosphoramidites are derivatives of saturated secondary amines.

Abstract: A new class of nucleoside phosphoramidites which are relatively stable to permit isolation thereof and storage at room temperature. The phosphoramidites are derivatives of saturated secondary amines.

Abstract: A new class of nucleoside phosphoramidites which are relatively stable to permit isolation thereof and storage at room temperature. The phosphoramidites are derivatives of saturated secondary amines.