Abstract: L-nucleosides are conformationally constrained by at least one additional ring formed by a bridge connecting at least two atoms within a sugar moiety of the nucleoside. While a single additional ring is formed by bridging C1-C4 atoms, two additional rings are formed by bridging both C1-C2, and C3-C4 atoms, or C1-C3 and C2-C4 atoms by bridges having the general structure A—B—Z. The conformationally constrained nucleosides may be incorporated into oligonucleotides and dinucleotides, and it is contemplated that compositions including the conformationally constrained nucleosides may have superior viral inhibitory or antineoplastic properties.

Abstract: Nucleoside analogues have structure (2) wherein Q is H or a sugar moiety or sugar analogue or a modified sugar or a nucleic backbone or backbone analogue, W is an alkylene or alkenylene chain of 0-5 carbon atoms, any of which may carry a substituent R8, X is O or N or NR12 or CR10, X′ is O or S or N, provided that when X′ is O or S, then X is C, Y is CH or N, R6 is NH2 or SMe or SO2Me or NHNH2, each of R7 and R8 is independently H or F or alkyl or alkenyl or aryl or acyl or a reporter moiety, R12 is independently H or alkyl or alkenyl or aryl or acyl or a reporter moiety, and R10 is H or ═O or F or alkyl or aryl or a reporter moiety.

Abstract: The present invention relates to the use of self-assembled monolayers with mixtures of conductive oligomers and insulators to detect target analytes.

Abstract: A synthesis of [2.2.1]bicyclo nucleosides which is shorter and provides higher overall yields proceeds via the key intermediate of the general formula III, wherein R4 and R5 are, for instance, sulfonates and R7 is, for instance, a halogen or an acetate. From compounds of the general formula II, such as 3-O-aryl-4-C-hydroxymethyl-1,2-O-isopropylidene-&agr;-D-ribofuranose, intermediates of the general formula III are suitable for coupling with silylated nucleobases. Upon one-pot base-induced ring-closure and desulfonation of the formed [2.2.1]bicyclo nucleoside, a short route to each the LNA (Locked Nucleic Acid) derivatives of adenosine, cytosine, uridine, thymidine and guanidine is demonstrated. The use of the 5′-sulfonated ring-closed intermediate also allows for synthesis of 5′-amino- and thio-LNAs.

Abstract: The present invention relates to anti-tumor compounds, compositions and methods. In particular, the invention relates to indolocarbazole analogues of the following general formulas that inhibit topoisomerase I activity.

Abstract: The present invention relates to a novel process to make indolocarbazole glycosides in high purity which inhibit the growth of tumor cells and are therefore useful in the treatment of cancer in mammals, and the like.

Abstract: The present invention relates to a novel glycosidation process to make intermediates useful in the preparation of indolopyrrolocarbazole derivatives which inhibit the growth of tumor cells and are therefore useful in the treatment of cancer in mammals, and the like.

Abstract: Methods for selectively protecting the exocyclic amino function of a purine nucleoside are provided using activating agents to effect acylation at the exocyclic amino site. Methods are also provided for recycling polymer bound coupling supports from the reaction mixtures produced upon N-acylation.

Abstract: This invention relates to a process for preparation of an indolopyrrolocarbazole derivative [I] by treating a compound [V] with a base in an inert solvent to prepare a compound [IV], reacting the obtained compound [IV] with a compound [III] to prepare a compound [II] and then removing the protective groups of the compound [II], the preparation intermediates compound [II], compound [III] and compound [IV], and processes for preparation of the compound [III].

Abstract: Propargylethoxyamino nucleosides are disclosed having the structure wherein R1 and R2 are —H, lower alkyl, or label; B is a 7-deazapurine, purine, or pyrimidine nucleoside base; W1 is —H or —OH; W2 is —OH or a moiety which renders the nucleoside incapable of forming a phosphodiester bond at the 3′-position; and W3 is —PO4, —P2O7, —P3O10, phosphate analog, or —OH. Additionally, a primer extension method is provided employing the above propargylethoxyamino nucleosides.

Abstract: Modified nucleosides and methods of making and using the nucleosides are disclosed. The compounds can be prepared by reacting nucleoside starting materials that contain a suitable leaving group at one or more of the carbon atoms in the purine or pyrimidine ring, with a vinylstannane, carbon monoxide, and a palladium catalyst to provide 1-ene-3-one intermediates. These intermediates are then reacted with suitably functionalized primary or secondary amines via a Michael reaction. When the intermediate is a 5-position modified pyrimidine ring, and the amine contains a second hydrogen, it can do a second Michael reaction with the ene-one or the ene-imine in the pyrimidine ring. Appropriate modification of the amine reactant can yield products with various bioactivities. The nucleosides can be used therapeutically as anti-cancer, anti-bacterial or anti-viral drugs. The nucleosides can also be used for diagnostic applications, for example, by incorporating a radiolabel or fluorescent label into the molecule.

Abstract: A process for the purification of nucleosides, and more particularly to a selective solvent extraction method for purifying protected nucleosides. In the purification process, solid particles of protected nucleosides are selectively washed to remove undesirable polar and/or non-polar impurities, while leaving the solid particles substantially undissolved.

Abstract: Methods for the regioselective alkylation at the 2′-hydroxy position over the 3′-hydroxy position of nucleosides and nucleoside analogs, forming 2′-O-ester modified compounds, are disclosed. Reduction and derivatization of the 2′-O-ester provides 2′-O-modified nucleosides and nucleoside analogs useful for the synthesis of oligomeric compounds having improved hybridization affinity and nuclease resistance.

Abstract: The present invention discloses improved methods for oligonucleotide synthesis and purification. In the methods of the invention, a half-life is determined for deprotection of the 5′-OH protecting group at the 5′-terminus of an oligonucleotide post-synthesis. The half-life is used to determine an optimal reaction time for removal of the 5′-OH protecting group. The methods of the invention are amenable to the large-scale synthesis and purification of oligonucleotides.

Abstract: The present invention provides novel methods for preparing oligonucleotide conjugates using a novel electrophilic haloacetyl linker. Novel compounds and intermediates are also disclosed.

Abstract: Tetrahydrofuranyl compounds are provided that are functionalized to include pendant conjugate groups, and which are useful in diagnosis assays and as research reagents. Novel intermediates for the synthesis of the compounds are also provided.

Abstract: Nucleoside analogues containing the degenerate base analogue P and derivatives thereof are provided with reporter moieties preferably comprising signal moieties. The nucleoside analogues are useful for labeling DNA or RNA or for incorporating in oligonucleotides.

Abstract: The invention relates to compositions comprising acyl derivatives of 2′-deoxyribonucleosides. The invention also relates to methods of treating or preventing radiation, mutagen and sunlight-induced biological damage, and methods for improving wound healing and tissue repair, comprising administering the compositions of the present invention to an animal.

Abstract: The invention relates to compositions comprising acyl derivatives of 2′-deoxyribonucleosides. The invention also relates to methods of treating or preventing radiation, mutagen and sunlight-induced biological damage, and methods for improving wound healing and tissue repair, comprising administering the compositions of the present invention to an animal.

Abstract: The present invention relates, in general, to AAMP-1, and to a peptide derived from the amino-terminal region of AAMP, P189. In particular, the present invention relates to a DNA segment encoding AAMP-1, P189 or fragments thereof; polypeptides encoded by said DNA segment; recombinant DNA molecules containing the DNA segment; cells containing the recombinant DNA molecule; a method of producing a AAMP-1, and P189 polypeptide or fragments thereof; antibodies specific to AAMP-1; and a method of measuring the amount of AAMP-1 in a sample. The present invention further relates to methods of using AAMP, P189 or fragments thereof in promoting cell-cell or cell-substrate adhesion, wound healing in patients, prosthetic acceptance, concentrating heparin in tissues, and inhibiting metastases and invasion of malignant cells.

Abstract: Synthetic processes are provided wherein mixed backbone oligomeric compounds are prepared having at least one phosphodiester intemucleoside linkage in addition to one or more phosphorothioate, phosphoramidate and boranophosphate internucleoside linkages. Novel H-phosphonate intermediates are also disclosed that are useful in the synthetic processes. The synthetic processes use a novel oxidation step to oxidize H-phosphonate internuleoside linkages to phosphodiester internuleoside linkages without degradation of adjacent phosphorothioate, phosphoramidate and boranophosphate internucleoside linkages. Also provided are synthetic intermediates useful in such processes.

Abstract: This disclosure relates to a method of specifically decorating selected mammalian chromosomes and of detecting, identifying and and/or quantitating selected individual chromosomes, by means of chromosomal in situ suppression (CISS) hybridization. The method is useful in analyzing cells for the occurrence of chromosomes, chromosome fragments or chromosome aberrations.