Abstract: Apparatus and methods are described for split synthesis combinatorial chemistry that provides candidate libraries where an even distribution of theoretical products is obtainable through even mixing during the pooling step, followed by controlled redistribution of the mixed pooled products from the prior addition step into separate synthesis columns, one for each different specie of subunit to be added.

Abstract: The present invention includes the selection and isolation of thioaptamers that target the ribonuclease domains of enzymes, e.g., HIV reverse transcriptase.

Abstract: The present invention includes thioaptamers that are partially thio-modified, methods and compositions for the isolation, selection, improvement, characterization and use of RNA and DNA thioaptamers for gene silencing, including degradative and non-degradative interference with translation.

Abstract: The present invention includes composition and methods for making and using a combinatorial library to identify thioaptamers that bind to targets on or about pathogens. Compositions, kits and methods are also provided for the identification of pathogens, e.g., viral, bacterial or other proteins related infectious disease, as well as, vaccines and vaccine adjuvants are provided that modify host immune responses.

Abstract: The present invention includes the selection and isolation of thioaptamers that target the signaling protein TGF-?1, compositions of such thioaptamers and the use of such thioaptamers to either block or enhance signal transduction of the TGF-?1 protein and thus function as, e.g., immunomodulatory agents. Thioaptamers may also be targeted alone or in combination with other thioaptamers against the ligand, the receptors, the ligand trap protein(s) and/or the co-receptors to modulate TGF-? signaling pathway.

Abstract: The present invention provides a method for concurrent achiral nucleotide modification and amplification using PCR. Provided by this method are NF-kB specific thioaptamers of novel sequence. This invention further provides methods of post-selection aptamer modification wherein one or more selected nucleotides of aptamers of known sequence are substituted with modified achiral nucleotides, particularly achiral thiophosphate nucleotides, wherein the substitution results in increased nuclease resistance while retaining binding efficiency and selectivity. Thiosubstitution of post-selection aptamers with specificity for the nuclear factor, NF-?B, produced in accordance with this method have increased binding affinity and specificity in addition to nuclease resistance. Also provided are methods for fractionating oligonucleotides depending on their degree of thiosubstitution by anion exchange chromatography.

Abstract: The present invention includes composition and methods for making and using a combinatorial library having two or more beads, wherein attached to each bead is a unique nucleic acid aptamer that have disposed thereon a unique sequence. The library aptamers may be attached covalently to the one or more beads, which may be polystyrene beads. The aptamers may include phosphorothioate, phosphorodithioate and/or methylphosphonate linkages and may be single or double stranded DNA, RNA or even PNAs.

Abstract: A system and method for determining the effect of a target molecule within a physiological pathway is disclosed in which a thioaptamer is used to affect a detectable activity of the physiological pathway in a cell or cell fragment.

Abstract: A method for synthesis of oligonucleotide analogs having dithiophosphate internucleosidic linkages is described. Monohalohydrocarbylthiophosphoramidites are utilized to prepare nucleoside thiophosphoramidite intermediates which are activated for nucleoside coupling with tetrazole catalysts. Sulfur oxidation and dehydrocarbylation of the coupled thiophosphite intermediates provide oligonucleotide analogs having achiral dithiophosphate internucleosidic linkages.