Abstract: A process of manufacturing protected nucleosides comprises reacting a nucleoside with a protecting reagent in the presence of a regioselective activator to produce a regioselectively protected nucleoside. In some embodiments of the inventive method, an optionally substituted trityl or optionally substituted pixyl group is selectively added to the 5?-O-position of a nucleoside in the presence of lutidine as activator or activator/solvent. The inventive method results in improved selectivity of the 5?-O-position over the 3?-O-position, thereby improving overall product yield and purity, and permitting simplified purification protocols, in some cases obviating the need for chromatography to produce a purified protected nucleoside suitable for automated synthesis of oligonucleotides, such as primers, probes and antisense molecules.

Abstract: Mixtures of chemical compounds are provided having antibacterial and other utility. The mixtures are formed, preferably in solution phase, from the reaction of a purine or pyrimiding heterocyclic scaffold with a set of related chemical substituients, optionally through employment of a tether moiety. Libraries formed in accordance with the invention have utility per se and are articles of commerce. They can be used to screen for pesticides, drugs and other biologically active compounds.

Abstract: The present invention is directed to nucleoside monomers wherein the 3?-O atom is replaced with a methylene group. The present invention also provides oligomers comprising a plurality of such monomers which are linked by methylene phosphonate linkages. Further, methods of preparing monomers and oligomers according to the present invention are provided.

Abstract: Methods for the identification of compounds which modulate, either inhibit or stimulate, biomolecules are provided. Nucleic acids, especially RNAs are preferred substrates for such modulation. The present methods are particularly powerful in that they provide novel combinations of techniques which give rise to compounds, usually “small” organic compounds, which are highly potent modulators of RNA and other biomolecular activity. In accordance with preferred aspects of the invention, very large numbers of compounds may be tested essentially simultaneously to determine whether they are likely to interact with a molecular interaction site and modulate the activity of the biomolecule. Pharmaceuticals, veterinary drugs, agricultural chemicals, industrial chemicals, research chemicals and many other beneficial compounds may be identified in accordance with embodiments of this invention.

Abstract: A process for removing a phosphorus protecting group from a protected phosphate triester or phosphorothioate triester includes contacting a protected phosphate or phosphorothioate triester with a thiol compound that is not offensive to the olfactory senses.

Abstract: Compounds having particular interest as labels and various novel uses in diagnostics and therapeutics are provided which have structure (1) wherein R1 is a binding partner, a linker or H; a and b are 0 or 1, provided that the total of a and b is 0 or 1; A is N or C; X is S, O, —C(O)—, NH or NCH2R6; Y is —C(O)—; Z is taken together with A to form an aryl or heteroaryl ring structure comprising 5 or 6 ring atoms wherein the heteroaryl ring comprises a single O ring heteroatom, a single N ring heteroatom, a single S ring heteroatom, a single O and a single N ring heteroatom separated by a carbon atom, a single S and a single N ring heteroatom separated by a carbon atom, 2 N ring heteroatoms separated by a carbon atom, or 3 N ring heteroatoms at least two of which are separated by a carbon atom, and wherein the aryl or heteroaryl ring carbon atoms are unsubstituted with other than H or at least 1 nonbridging ring carbon atom is substituted with R6 or ?O; R6 is independently H, C1-C6 alkyl, C2-C6 alkenyl, C

Abstract: The present invention is directed to analogs of aminoglycoside compounds of the class having a glycosylated 2-deoxystreptamine (2-DOS) ring as well as their preparation and use as prophylactic or therapeutics against microbial infection. Compounds of the invention comprises at least one aryl, heteroaryl, substituted aryl or substituted heteroaryl group in place of a glycosyl group attached to the 2-deoxystreptamine ring.

Abstract: Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be incorporated into pharmaceutically acceptable carriers and can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention.

Abstract: Compounds having structure (1) wherein R1 is —H a protecting group, a linker or a binding partner; and R2 and R34 are as defined in the specification. The invention also provides intermediates and methods make the structure (1) compounds, as well as methods to use the compounds as labels in diagnostic assays and to enhance binding to complementary bases.

Abstract: 2?-O-(2-Methylthioethyl), has been incorporated into oligonucleotides and evaluated for antisense properties in comparison with the known 2?-O-(2-methoxyethyl) 2?-O-MOE modification. The 2?-O-MTE modified oligonucleotides exhibit improved binding to human serum albumin compared with the 2?-O-MOE modified oligonucleotides and maintain high binding affinity to target RNA.

Abstract: Linked nucleosides having at least one functionalized nucleosid that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2?-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining linked nucleosides are 2?-deoxy-2?-fluoro, 2?-O-methoxy, 2?-O-ethoxy, 2?-O-propoxy, 2?-O-aminoalkoxy or 2?-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3? or the 5? positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.

Abstract: Methods for the preparation of oligonucleotides having bioreversible phosphate blocking groups are disclosed. In one aspect, the present invention provides compounds comprising a sequence of nucleotide units that includes a first segment having at least one internucleoside linkage of formula: 3?-O—P(X)(O?)—O-5? and a second segment having at least one internucleoside linkage of formula: 3?-O—P(X)(Y1—(CH2)q—Y2—Y3—Z)—O-5? wherein each of X, Y1, and Y2 is, independently, O or S; q is 2 to about 4; Y3 is C(?O) or S; and Z is aryl having 6 to about 14 carbon atoms or alkyl having from one to about six carbon atoms.

Abstract: Oligomers which have substituents on the 2? position are resistant to oligonucleases and furthermore can be derivatized to deliver reagents or drugs, to carry label, or to provide other properties.

Abstract: Nucleotides and oligonucleosides functionalized to include alkylamino functionality, and derivatives thereof. In certain embodiments, the compounds of the invention further include steroids, reporter molecules, reporter enzymes, lipophilic molecules, peptides or proteins attached to the nucleotides through the alkylamino group.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of CoREST. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding CoREST. Methods of using these compounds for modulation of CoREST expression and for treatment of diseases associated with expression of CoREST are provided.

Abstract: Therapeutic oligonucleotide analogues which have improved nuclease resistance and improved cellular uptake are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in natural oligomers with four atom linking groups forms unique di- and poly-nucleosides and nucleotides useful in regulating RNA expression and in therapeutics. Methods of synthesis and use are also disclosed.

Abstract: Mixtures of chemical compounds are provided having antibacterial and other utility. The mixtures are formed, preferably in solution phase, from the reaction of a purine or pyrimiding heterocyclic scaffold with a set of related chemical substituients, optionally through employment of a tether moiety. Libraries formed in accordance with the invention have utility per se and are articles of commerce. They can be used to screen for pesticides, drugs and other biologically active compounds.

Abstract: Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be incorporated into pharmaceutically acceptable carriers and can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention.

Abstract: Synthetic processes are provided for the solution phase synthesis of oligonucleotides, especially phosphorothioate oligonucleotides, and intermediate compounds useful in the processes. Intermediates having structure are prepared in accord with preferred embodiments.

Abstract: Novel chiral compounds that mimic and/or modulate the activity of wild-type nucleic acids are disclosed. In general, the compounds are phosphorothioate oligonucleotides wherein the 5?, and the 3?-terminal internucleoside linkages are chirally Sp and internal internucleoside linkages are chirally Rp.