摘要:
Polynucleotides comprising molecular interaction sites of 16S rRNA that have particular secondary structure are provided. Methods of using such polynucleotides to screen, virtually or actually, combinatorial libraries of compounds that bind thereto are also provided. Method of modulating the activity of 16S rRNA by contacting 16S rRNA or prokaryotic cells containing the same with a compound identified by such virtual or actual screening are also provided.
摘要:
The present invention provides methods for the identification of target molecules that bind to ligands, particularly microRNA ligands and mimics thereof and/or microRNA target molecules and mimics thereof, with as little as millimolar (mM) affinity using mass spectrometry. The methods may be used to determine the mode of binding interaction between two or more of these target molecules to the ligand as well as their relative affinities. Also provided are methods for designing compounds having greater affinity to a ligand by identifying two or more target molecules using mass spectrometry methods of the invention and linking the target molecules together to form a novel compound.
摘要:
The present invention provides methods for the determination of the structure of biomolecular targets, as well as the site and nature of the interaction between ligands and biomolecular targets. The present invention also provides methods for the determination of the relative affinity of a ligand for the biomolecular target it interacts with. Also provided are methods for screening ligand or combinatorial libraries of compounds against one or more than one biological target molecules. The methods of the invention also allow determination of the relative binding affinity of combinatorial and other compounds for a biomolecular target. The present invention further provides methods for the use of mass modifying tags for screening multiple biomolecular targets. In a preferred embodiment, ligands which have great specificity and affinity for molecular interaction sites on biomolecules, especially RNA can be identified. In preferred embodiments, such identification can be made simultaneously with libraries of ligands.
摘要:
Compositions and methods for modulating the activity of RNA are disclosed, In accordance with preferred embodiments, antisense compositions are prepared targeting reactive portions. The reactive portions preferably comprise one or two imidazole functionalities conjugated to the targeting oligonucleotide via linkers with or without intervening intercalating moieties. Therapeutics, diagnostics and research methods also are disclosed, as are synthetic nucleosides and nucleoside fragments that can be elaborated into oligonucleotides.
摘要:
Methods of identifying molecular interaction sites in eukaryotic and prokaryotic nucleic acids, especially RNA, are described. Secondary structural elements are identified from highly conserved sequences. Methods of preparing databases relating to such molecular interaction sites are also provided herein as are databases themselves. Therapeutic, agricultural, industrial, and other applicability results from interaction of such molecular interaction sites with “small” and other molecules.
摘要:
Methods are provided for detection and quantitation of mixtures containing target nucleobase sequences using capillary electrophoresis. Peptide nucleic acid oligomers, complementary to the target sequences and preferably having appended detectable labels, are hybridized to the targets. Capillary electrophoresis is then performed, and the detectable label is detected and quantitated.
摘要:
The present disclosure relates to methods for identifying proteins or peptide motifs of intracellular, extracellular, or extracellular matrix proteins specifically exposed in wound sites, as well as compositions for treating wounds, and methods for their use.
摘要:
Methods of identifying molecular interaction sites in eukaryotic and prokaryotic nucleic acids, especially RNA, are described. Secondary structural elements are identified from highly conserved sequences. Methods of preparing databases relating to such molecular interaction sites are also provided herein as are databases themselves. Therapeutic, agricultural, industrial, and other applicability results from interaction of such molecular interaction sites with “small” and other molecules.
摘要:
Methods for detecting and identifying unknown bioagents, including bacteria, viruses and the like, by a combination of microRNA containing nucleic acid amplification and molecular weight determination using primers which hybridize to conserved sequence regions of microRNA containing nucleic acids derived from a bioagent and which bracket variable sequence regions that uniquely identify the bioagent. The result is a “base composition signature” (BCS) or molecular mass which is then matched against a database of base composition signatures or molecular masses, by which the species of the bioagent is identified.
摘要:
The present disclosure is related to improved systems and methods for delivering samples for high-throughput mass spectrometric analysis to an atmospheric-pressure ionization source. In an exemplary embodiment, the system includes a solvent reservoir for storing a solvent solution, a first valve which is coupled to the solvent reservoir, first and second pumps for delivering solvent solution and which are coupled to the first valve and which the delivery flow rate of the first pump is greater than the delivery flow rate of the second pump, an injection system having a sample injector and an second valve which is coupled to the first valve and which is capable of being coupled to can be couple to an electrospray ionization source. In another embodiment, the system can also include an atmospheric-pressure ionization chamber, an atmospheric-pressure ionization sprayer and a nebulizer gas source and a voltage supply source. In yet another embodiment, the system may further include a puffer valve that is coupled to the nebulizer gas source and the atmospheric-pressure ionization sprayer and a gas puffer that is coupled to the puffer valve. A distal end of the gas puffer may be located within the atmospheric-pressure ionization chamber and aligned with the distal end of the atmospheric-pressure ionization sprayer and the puffer valve may control the delivery of the nebulizer gas to the atmospheric-pressure ionization sprayer and the gas puffer.