Chiron Corporation

Bayer Corporation

Other

Novartis Vaccines & Diagnostics, Gmbh

Thomas Horn

Michael S Urdea

Brian David Warner

Chu-an Chang

Mark L Collins

Patrick J Sheridan

Timothy J Fultz

Ronald N Zuckermann

Janice A Kolberg

Joyce A Running

Jennifer M Clyne

Ray Sanchez-Pescador

Robert L Letsinger

Say-Jong Law

Ellen H Fiss

Todd B Sells

Hartmut Schroeder

Michael S Ureda

Tanjore N Balasubramaniam

Molecules having potential biological activity, particularly peptoids, that are conjugated to solid phase supports, spacer groups, and/or ligation moieties, and methods of their preparation, are described. In some instances, the molecules of the invention are made entirely by solid phase synthesis. In other instances, the spacer groups are hydrophilic and compositions containing them, and to solid phase synthesis of varied structure peptoids using chemoselective ligation moieties.

Peptoids incorporating chemoselective functionalities

Purification of oligomers using dual-end selection

Methods are provided for reducing background signals encountered in nucleic acid hybridization assays and other assays that involve hybridization of a labeled oligomer to its complement. The method is premised on the significant reduction of signal generation that occurs when a quenchable dye-labeled oligomer forms a hybrid complex. In addition, a method is provided for enhancing the detectable signal emitted from an amplification multimer hybridized to an oligomer probe to which a quenchable dye has been conjugated through a linker such that the emission from the dye is not quenched upon hybrid complex formation. Novel oligonucleotide probes are also provided that comprise an oligomer to which has been directly or indirectly through a linker a quenchable dye.

Oligonucleotide probes bearing quenchable fluorescent labels, and methods of use thereof

Methods are provided for substantially reducing background signals encountered in nucleic acid hybridization assays. The method is premised on the elimination or significant reduction of the phenomenon of nonspecific hybridization, so as to provide a detectable signal which is produced only in the presence the target polynucleotide of interest. In addition, a novel method for the chemical synthesis of isoguanosine or 2&prime;-deoxy-isoguanosine is provided. The invention also has applications in antisense and aptamer therapeutics and drug discovery.

Reduction of nonspecific hybridization by using novel base-pairing schemes

Branched polymers and multiply connected macromolecular structures are provided, wherein the polymers and structures are provided, wherein the polymers are structures comprise at least two branches and/or macrocycles, at least one of which is a target binding moiety capable of binding to a target molecule of interest, and at least another of which is a signal generation moiety capable of directly or indirectly generating a signal. These polymers and structures contain components that are linked through sulfur-containing bridges that are selectively cleaved by oxidation, e.g. thiophosphorylacyl, dithiophosphorylacyl, thiophosphorylthio, thiophosphorylalkylamino and/or dithiophosphorylalkylamino bridges, Synthetic methods are also provided, as are kits containing a complexing buffer and a nucleic acid probe composed of the branched polymer or macromolecular structure.

Synthesis of branched nucleic acids

Novel oligonucleotides are provided having cationic internucleoside linkages. The cationic internucleoside linkage has the structure ##STR1## wherein W, X, Y, Z, R.sup.1, R.sup.2, and R.sup.3 are as defined herein, P* represents an asymmetric phosphorus atom capable of existing in two distinct stereoisomeric configurations, and further wherein the internucleoside linkage is stereouniform. Certain of these oligonucleotides may have alternating anionic and cationic internucleoside linkages, which are not necessarily stereouniform. A method for synthesizing the compounds are provided as well, as are methods for using the compounds, e.g., as antisense molecules and in nucleic acid hybridization assays.

Cationic oligonucleotides, and related methods of synthesis and use

Comb-type branched polynucleotides are used as amplification multimers in nucleic acid hybridization assays.

Nucleic acid hybridization assays employing large comb-type branched

Methods are provided for substantially reducing background signals encountered in nucleic acid hybridization assays. The method is premised on the elimination or significant reduction of the phenomenon of nonspecific hybridization, so as to provide a detectable signal which is produced only in the presence the target polynucleotide of interest. In addition, a novel method for the chemical synthesis of isoguanosine or 2'-deoxy-isoguanosine is provided. The invention also has applications in antisense and aptamer therapeutics and drug discovery.

Reduction of nonspecific hybridization by using novel base-pairing

Large comb-type branched polynucleotides useful as amplifier molecules in nucleic acid hybridization assays are provided, the polynucleotides comprising: a polynucleotide backbone having at least about 15 multifunctional nucleotides, each of which defines a sidechain site and a first single-stranded oligonucleotide unit that is capable of binding specifically to a first single-stranded polynucleotide sequence of interest; and pendant polynucleotide sidechains extending from said multifunctional nucleotides each comprising iterations of a second single-stranded oligonucleotide unit that is capable of binding specifically to a second single-stranded polynucleotide sequence of interest, the total number of iterations in all sidechains being at least 20. Methods of making these polynucleotides are also provided.

Large comb type branched polynucleotides

A method for binding a target polynucleotide in a sample is provided. The method uses an assay reagent which is a substrate noncovalently bound to a hydrophobic moiety which is part of a polynucleotide capture probe. This assay reagent is contacted with the sample under conditions which permit hybridization between said capture probe and said target polynucleotide, thereby binding the target polynucleotide.

Hydrophobic nucleic acid probe

Hydroxyl-protecting groups orthogonally removable by reduction with a liquid reducing agent are disclosed. The novel hydroxyl-protecting groups are particularly useful in the chemical synthesis of linear and branched oligonucleotide structures, as they are readily removed from the protected molecule with mild reagents such as dithionite. Examples of such hydroxyl-protecting groups include the 2-methylene-9,10-anthraquinone (Maq) carbonate ester and the p-nitrobenzyl carbonate ester.

Oligonucleotides containing hydroxyl-protecting groups orthogonally

Linear or branched oligonucleotide multimers useful as amplifiers in biochemical assays which comprise (1) at least one first single-stranded oligonucleotide unit that is complementary to a single-stranded oligonucleotide sequence of interest, and (2) a multiplicity of second single-stranded oligonucleotide units that are complementary to a single-stranded labeled oligonucleotide. Amplified sandwich nucleic acid hybridizations and immunoassays using the multimers are exemplified.

Growing community of inventors

Berkeley, CA, United States of America

Thomas Horn