296 results about "Protein targeting" patented technology

The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins that are degraded and / or otherwise inhibited by bifunctional compounds of the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand that binds to the ubiquitin ligase and on the other end a moiety that binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds of the present invention, consistent with the degradation / inhibition of targeted polypeptides.

Some embodiments disclosed herein provide a plurality of compositions each comprising a protein binding reagent conjugated with an oligonucleotide. The oligonucleotide comprises a unique identifier for the protein binding reagent it is conjugated with, and the protein binding reagent is capable of specifically binding to a protein target. Further disclosed are methods and kits for quantitative analysis of a plurality of protein targets in a sample and for simultaneous quantitative analysis of protein and nucleic acid targets in a sample. Also disclosed herein are systems and methods for preparing a labeled biomolecule reagent, including a labeled biomolecule agent comprising a protein binding reagent conjugated with an oligonucleotide.

The present invention is based on the discovery that proteins produced in insect cell cultures are glycosylated in a unique manner that causes them to be selectively imported by cells that express mannose receptors on their membranes, particularly macrophages. Proteins that are selectively imported into cells containing mannose receptors are provided, as well as pharmaceutical compositions containing such proteins and methods for producing such proteins. Application of the present invention to produce proteins useful for treating lysosomal storage disorders is also disclosed. Engineering of cells to express mannose receptors so that they will selectively import proteins produced in insect cells is also taught, as well as a protein targeting system using such cells and proteins. Finally, an improved elution buffer for the purification of proteins produced in insect cells from a Concanavalin A column is provided.

Methods are provided for efficient, high throughput screening of antibody libraries against proteins targets, especially membrane proteins. In particular, methods are provided for screening a fully human antibody library against membrane proteins such as HIV coreceptors in yeast. More particularly, a library of human single chain antibodies is screened against peptide fragments derived from extracellular domains of human CCR5 and high affinity monoclonal antibodies against CCR5 are selected.

The present invention relates to the use of proteins that are differentially expressed in primary brain tumor tissues, as compared to normal brain tissues, as biomolecular targets for brain tumor treatment therapies. Specifically, the present invention relates to the use of therapeutic and imaging agents, which specifically bind to one or more of the identified brain tumor protein targets. The present invention also provides compounds and pharmaceutically acceptable compositions for administration in the methods of the invention. Nucleic acid probes specific for the spliced mRNA encoding these variants and affinity reagents specific for the novel proteins are also provided.

The present application discloses acolloidal nanoparticle that includes a therapeutic nucleic acid species and a targeting protein species attached via a coating on the nanoparticle that facilitates the specific attachment of both species.

Mass spectrometry-based methods are described for the detection or quantification of targeted proteins in biological samples e.g., plants, animals, and microorganisms, parts (e.g., tissue or cells) thereof, and products derived from plants, animals or microorganisms.

One aspect of the invention provides a method of diagnosing a disease condition, comprising measuring presence or amount of a targeted protein or a degradation product of said protein in a collected biological sample as a marker for the disease condition. The targeted protein or degradation product is selected for measurement based on a prior identification of a measurable half-life at a predetermined time period, including the time at which said method is conducted, and correlating said measuring with the presence or absence of the disease condition. The targeted protein or degradation product may be identified by selecting a protein known or suspected to be a diagnostic marker for the disease condition, analyzing degradation of the protein in the collected biological sample, and selecting a protein or degradation product that exhibits a measurable half-life at a predetermined period of time. The analyzing may include identifying degradation product(s) of the protein as a function of time, and half-life of the protein and the degradation product(s).

This invention relates to novel fusion proteins which are comprised of a targeting protein that binds tissue factor (TF), which is operably linked to the thrombomodulin (TM) EGF456 domain alone or in combination with at least one other TM domain selected from the group consisting of the N-terminal hydrophobic region domain, the EGF123 domain, the interdomain loop between EGF3 and EGF4, and the O-glycosylated Ser / Thr-rich domain, or analogs, fragments, derivatives or variants thereof. The fusion protein binds at the site of injury and prevents the initiation of thrombosis. The fusion protein can be used to treat a variety of thrombotic conditions including but not limited to deep vein thrombosis, disseminated intravascular coagulation, and acute coronary syndrome.

This invention relates to novel fusion proteins which are comprised of a targeting protein that binds tissue factor (TF), which is operably linked to the thrombomodulin (TM) EGF456 domain alone or in combination with at least one other TM domain selected from the group consisting of the N-terminal hydrophobic region domain, the EGF123 domain, the interdomain loop between EGF3 and EGF4, and the O-glycosylated Ser / Thr-rich domain, or analogs, fragments, derivatives or variants thereof. The fusion protein binds at the site of injury and prevents the initiation of thrombosis. The fusion protein can be used to treat a variety of thrombotic conditions including but not limited to deep vein thrombosis, disseminated intravascular coagulation, and acute coronary syndrome.

This invention is in the area of compositions and methods for regulating chimeric antigen receptor immune effector cell, for example T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation.

The invention comprises systems, methods and arrays for identification and optimization of novel peptide binders to protein targets. Embodiments include steps of peptide binder discovery, core peptide maturation, N-terminal and C-terminal extension and kinetics analysis of the final peptide binder.

The present invention relates to novel compositions of methotrexate-containing heterodimeric probe molecules, also known as chemical inducers of dimerization (CID), useful in three-hybrid assays. The invention further relates to synthesis of said compositions and their intermediates. Another aspect of the invention is a method for using the heterodimeric probe molecules described herein in drug screens to identify potential protein targets to a given ligand, optimize protein-ligand interactions, or identify potential ligands for a given protein target. In certain embodiments, the invention contemplates the synthesis of the following methotrexate-containing heterodimeric probe:

The invention relates to a method and a system for predicting a protein interaction target point of a drug. The method comprises: 1) collecting a human protein interaction network and single protein target point data of the drug, and constructing an interactive protein target point data set of the drug; 2) obtaining description data of the drug and proteins; 3) constructing a bigraph for representing an interactive relationship between the drug and a protein pair, constructing a similar matrix for representing drug similarity and protein pair similarity, establishing a kernel function for correlating the similar matrix of the drug and the protein pair, and establishing a prediction model through a machine learning algorithm; and 4) performing independent set testing by utilizing unknown drug and interactive protein pair, and predicting a possibly existent unknown drug protein interaction target point, and verifying a prediction result through database and document retrieval. According to the method and the system, the search space of the drug target point can be expanded and the more specific drug protein interaction target point with the best classification performance can be obtained.

The invention discloses a universal construction method for a protein-targeting chimeric molecule compound. The objective of the invention is to provide a method for adjusting the level of proteins by degrading the proteins through targeted ubiquitination. The construction method mainly comprises the following steps: 1) locating and analyzing a three-dimensional structure of a target protein and predicting active sites; 2) selecting a compound database; 3) virtually screening ligand compounds having high degrees of adaption to the target protein by using a computer; 4) acquiring the screened ligand compounds and screening an optimal ligand compound of the target protein through detection of interaction between micromolecules and the proteins; 5) constructing a protein-targeting chimeric molecule compound composed of the optimal ligand compound of the target protein, ubiquitin ligase E3 identification ligand and Linker connecting the optimal ligand compound of the target protein to the ubiquitin ligase E3 identification ligand by using a combination manner simulated by the computer; and 6) chemically synthesizing the protein-targeting chimeric molecule compound. With the method provided by the invention, the protein-targeting chimeric molecule compound can be rapidly and highly efficiently prepared, and specific degradation of intracellular target proteins is realized.

The present invention relates to a method capable of implementing on-target one-step desalination and enrichment of trace protein or polypeptide by means of combined application of hydrophobic polymer microblotting technique and matrix auxiliary laser analysis ionization mass spectrography. Said microblotting hydrophobic polymer has good adsorption and enrichment effect for protein and polypeptide, so that it can implement one-step desalination and direct MALDI-TOF-MS analysis. Said invention can be extensively used in the field of protein phylogeny.

A method of simultaneously co-purifying and concentrating nucleic acid and protein targets is described. The method includes automation of the entire sample preparation process, performed by having an analyst add a sample into a device that performs all of the steps necessary to prepare a sample for analysis. The method provides for samples that are not split during the sample preparation process and where common purification methods can be used for purifying multiple analytes.

The identification and evaluation of mRNA and protein targets associated with mRNP complexes and implicated in the expression of proteins involved in common physiological pathways is described. Effective targets are useful for treating a disease, condition or disorder associated with the physiological pathway.

The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain onone end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase toeffect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation / inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.

The identification and evaluation of mRNA and protein targets associated with RNA binding proteins or mRNP complexes is described. In particular, the invention provides methods for identifying RNA binding proteins associated with physiological pathways that participate in glucose and lipid metabolism and mRNAs that exhibit coordinated gene regulation across those M pathways. Candidate targets are provided that are useful for the diagnosis or treatment of diseases related to diseases, such as disease related to aberrant glucose and lipid metabolism, such as, for example, obesity, diabetes, and hypoglycemia.

Protein targets for disease intervention through inhibition of nucleic acid metabolism are disclosed. Novel polypeptides for one such target, DNA-dependent ATPase A, and novel polynucleotides encoding DNA-dependent ATPase A are disclosed. Phosphoaminoglycoside compounds which act on such protein targets to inhibit nucleic acid metabolism. In addition, screening assays for identifying compounds that inhibit nucleic acid-dependent ATPase activity, including, but not limited to, DNA-dependent ATPase A, are disclosed. Such compounds are useful in the treatment of diseases, including but not limited to cancer and infectious disease, through disruption of nucleic acid metabolism and induction of apoptosis. Moreover, methods for prevention and treatment of diseases including, but not limited to cancer and infectious disease are disclosed.

The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and / or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation / inhibition of targeted polypeptides.

The present invention discloses Resistance Management (RM) practices that are critical to safeguarding Bacillus thuringiensis as a natural resource and to sustaining genetically modified crops that express Bt toxins for managing ECB and WCRW. The methods involve blending seed transformed with a nucleic acid encoding a different pesticidal protein, where both proteins target the same pest, but use different modes of pesticidal action. The seed can be also treated with pesticidal agents.

Methods of synthesizing a peptide or peptide-like molecule to a polypeptide or protein target based on mode-matching each member of a set of peptide constituents of the peptide or peptide-like molecule to peptide constituents of the target polypeptide or protein target for treatment of neurological diseases.

A method of simultaneously co-purifying and concentrating nucleic acid and protein targets into a single volume is described. The method includes automation of the entire sample preparation process, performed by having an analyst add a sample into a device that performs all of the steps necessary to prepare a sample for analysis. The method provides for samples are not split during the sample preparation process and where common purification methods can be used for purifying multiple analytes.

Mass spectrometry-based methods are described for the detection or quantification of targeted proteins in biological samples e.g., plants, animals, and microorganisms, parts (e.g., tissue or cells) thereof, and products derived from plants, animals or microorganisms.

A protein is described. The protein comprises a lipid globule targeting sequence linked to a protein of interest (POI) wherein the targeting sequence comprises a hepatitis C virus (HCV) core protein or fragment or homologue thereof.

The present invention is related to analytical platforms and methods performed therewith for generating qualitative and / or quantitative protein expression profiles, in particular differential protein expression profiles, of cell populations comprising: generating lysates of one or more populations of cells, the lysates comprising a plurality of proteins expressed by the respective cell populations, providing an essentially planar solid support, depositing at discrete sites small quantities of the cell lysates, in diluted or undiluted form directly on said solid support or on an adhesion-promoting layer applied on said solid support, thereby creating one or more one- or two-dimensional arrays of discrete measurement areas on said solid support, applying a number of binding reagents as specific binding partners for the proteins contained in cell lysates in discrete measurement areas and to be detected and, if adequate, one or more detection reagents on said one or more arrays of measurement areas, the binding reagents and the detection reagents being applied sequentially or in a single addition-step, after binding of the detection reagents to the binding reagents, to the one or more arrays of discrete measurement areas for e.g. global analysis of signaling pathways or screening antibody sets / libraries against protein targets for best specificity, selectivity and affinity, and measuring and recording optical signals emanating from said one or more arrays of discrete measurement areas in a locally resolved manner, wherein said essentially planar solid support is non-porous and an optionally applied adhesion-promoting layer has a thickness of less than 1 μm.