Abstract: The present invention is a general method for inactivating or inhibiting ribonucleases. Ribonucleases are treated with a reducing agent and heat. RNA samples contaminated with ribonuclease may be treated with this method to protect them from degradation. The RNA may then be used directly in a variety of enzymatic reactions and molecular biology techniques. This method may also be applied to a variety of molecular biology reagents which may be contaminated with ribonuclease to protect an RNA from being degraded when incubated with the reagent.

Abstract: The present invention relates to methods for synthesizing an oligomeric compound on a solid support comprising contacting a solid support with a filling material to produce a mixture thereof; placing the mixture in a reaction vessel; and synthesizing the oligomeric compound. The present invention also relates to (a) reaction vessels for synthesizing oligomeric compounds comprising a solid support; and a filling material, (b) apparatuses for synthesizing oligomeric compounds comprising a reagent source, and a reaction vessel comprising a solid support; and a filling material, and (c) compositions comprising a solid support and a filling material mixed therewith.

Abstract: Novel hydrogen-phosphonodithioate compositions are provided which are particularly useful for forming internucleotide and internucleoside linkages in oligonucleosides or oligonucleotides. The oligonucleotides and analogs thereof made by using the hydrogen-phosphonodithioate compositions may be therapeutically useful as antiviral and anticancer agents and may have other therapeutic or diagnostic uses. A method for making the hydrogen-phosphonodithioates is provided as well as a method for converting same to an activated intermediate for substitution on the phosphorus atom.

Abstract: The invention provides lipophilic phosphonoacid/nucleoside conjugates that exhibit exceptional antiviral activity, including activity against drug-resistant HIV strains. Compounds of the invention include phosphonoacid/nucleoside conjugates where the carboxyl group and phosphonyl groups of the phosphonacid are esterified whereby the compound contains at least one lipophilic group and at least one nucleoside group.

Abstract: Nucleosidic monomers and oligomeric compounds prepared therefrom are provided which have increased nuclease resistance, substituent groups (such as 2′-aminooxy groups) for increasing binding affinity to complementary strand, and regions of 2′-deoxy-erythro-pentofuranosyl nucleotides that activate RNase H. Such oligomeric compounds are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to oligonucleotide therapeutics.

Abstract: The invention relates to a process for the preparation of a pyranosyl nucleic acid of the formula (I) or of the formula (II) The process for the preparation of the pyranosyl nucleic acid comprises (a) bonding the nucleoside to a solid support, (b) deprotecting the 3′,4′-protected nucleoside, (c) reacting the reaction product from step (b) with a 3′,4′-protected pyranosyl nuceloside phosphoramidite, repeating steps (b) and (c) one or more times to produce the desired length of nucleic acid, and coupling a biomolecule to the product of step (d). In a further step, the nucleic acid can be released from the solid support. In one embodiment, the biomolecule may be a DNA or RNA, where furanosyl nucleoside phosphoramidites are added to the pyranosyl nucleic acid.

Abstract: N6 heterocyclic 5′ modified adenosine derivatives that are adenosine A1 receptor partial or full agonists, and as such, are useful for modifying cardiac activity, modifying adipocyte function, treating central nervous system disorders, and treating diabetic disorders and obesity in mammals, and especially in humans.

Abstract: The invention provides synthons containing a novel carbamate internucleoside linkage, methods for using such synthons to make oligonucleotides containing such novel carbamate linkages, and oligonucleotides containing such novel carbamate linkages.

Abstract: This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside has the formula: wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted.

Abstract: Novel monocyclic L-Nucleoside compounds have the general formula Embodiments of these compounds are contemplated to be useful in treating a wide variety of diseases including infections, infestations, neoplasms, and autoimmune diseases. Viewed in terms of mechanism, embodiments of the novel compounds show immunomodulatory activity, and are expected to be useful in modulating the cytokine pattern, including modulation of Th1 and Th2 response.

Abstract: The invention provides new methods for synthesizing oligonucleotides that allow for deprotection of the oligonucleotides under more mild conditions than existing methods. The invention further provides a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups, as well as nucleoside synthons having such base protecting groups.

Abstract: An anticancer drug includes a compound represented by Formula (1): where R101 represents an acyl moiety of a saturated higher fatty acid, and R102 represents a hydrogen atom or an acyl moiety of a saturated higher fatty acid, and/or a pharmaceutically acceptable salt thereof.

Abstract: Novel purine L-nucleoside compounds are disclosed, in which both the purine rings and the sugar are either modified, functionalized or both. The novel compounds or pharmaceutically acceptable esters or salts thereof may be used in pharmaceutical compositions, and such compositions may be used to treat an infection, an infestation, a neoplasm, or an autoimmune disease. The novel compounds may also be used to modulate aspects of the immune system, including modulation of Th1 and Th2.

Abstract: Synthetic processes are provided wherein oligomeric compounds are prepared having phosphodiester, phosphorothioate, phosphorodithioate, or other covalent linkages. The oligomers have substantially reduced exocyclic adducts deriving from acrylonitrile or related contaminants.

Abstract: A method of capping a hydroxy group of a moiety, comprising coupling the moiety to a phosphor or phosphite derivative of a protected alcohol, so as to form the corresponding phosphate or phosphite between the hydroxy and phosphor or phosphite groups. The hydroxy group may be later de-capped by hydrolyzing the resulting compound to deprotect the protected alcohol and cleave the phosphate from the moiety so as to regenerate the hydroxy group of the moiety. The method has particular application to fabrication of addressable polynucleotide arrays and allows failed sequences, as well as inter-feature regions, to be left with a free hydroxy group at the ends of the molecules (failed sequences or linkers) at such locations.

Abstract: The present invention provides 2-aminopyridine and 2-pyridone C-nucleosides and oligonucleotides containing the subject nucleosides. The nucleosides are useful in the preparation of the subject oligonucleotides. The oligonucleotides are useful in oligonucleotide-based diagnosis and separation through triplex binding.

Abstract: This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside has the formula: wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted.

Abstract: 2-(3-,4-(substituted)-5-alkylthienyl)adenosines and the 5′-uronic acid amide analogues thereof having the following formula: are disclosed herein. Additionally disclosed are medicinal methods of treatment wherein the adenosine A2A agonist activity of the noted compounds stimulates mammalian coronary vasodilation for therapeutic purposes and for purposes of imaging the heart.

Abstract: The invention relates to a process for the preparation of vinyl pyrimidines of the formula I wherein R1 is hydrogen or a carboxylic ester group, and R2 is hydrogen or a group of the formula (a) wherein Ra is hydrogen, a protecting group or a group easily hydrolyzable under physiological conditions, by reacting a compound of the formula II wherein R21 is hydrogen or a group (a) wherein hydroxy groups are optionally protected, R3 is bromo, chloro or iodo, and R1 is as above, with a vinyl borane compound in the presence of a Pd complex and a base, and optionally, further reacting a product of formula I wherein R2 is hydrogen with a compound of the formula IV wherein Rb is a hydroxy protecting group and Z is a leaving group, in the presence of a Lewis acid catalyst.

Abstract: This invention is directed to a process for preparing N6-substituted adenosine derivatives, to intermediates useful therefor and to methods of preparing these intermediates.