344 results about "Protein degradation" patented technology

The invention relates to methods of treating protein degradation disorders, such cellular proliferative disorders (e.g., cancer) and protein deposition disorders (e.g., neurodegenerative disorders). The invention provides methods and pharmaceutical compositions for treating these diseases using aggresome inhibitors or combinations of aggresome inhibitors and proteasome inhibitors. The invention further relates to methods and pharmaceutical compositions for treating multiple myeloma. New HDAC / TDAC inhibitors and aggresome inhibitors are also provided as well as synthetic methodologies for preparing these compounds.

The present invention provides an array for rapidly identifying a host cell population capable of producing heterologous protein with improved yield and / or quality. The array comprises one or more host cell populations that have been genetically modified to increase the expression of one or more target genes involved in protein production, decrease the expression of one or more target genes involved in protein degradation, or both. One or more of the strains in the array may express the heterologous protein of interest in a periplasm compartment, or may secrete the heterologous protein extracellularly through an outer cell wall. The strain arrays are useful for screening for improved expression of any protein of interest, including therapeutic proteins, hormones, a growth factors, extracellular receptors or ligands, proteases, kinases, blood proteins, chemokines, cytokines, antibodies and the like.

A collection container and a method for collecting a biological sample, particularly whole blood, that includes at least one stabilizing agent in an amount effective to stabilize and inhibit protein degradation and / or fragmentation. The stabilizing agent is able to stabilize proteases in the biological sample, particularly at the point of collection, by inhibiting protein degradation and / or fragmentation in the sample when the sample is stored. The stabilizing agent includes one or more protease inhibitors.

Provided are bifunctional small molecules of Formula (I): or pharmaceutically acceptable salts thereof, wherein M represents a small organic molecule which binds, covalently or non-covalently, a kinase, such as Her3 protein kinase; L1 represents a linker; and RH represents a hydrophobic group. An example of a compound of Formula (I) is a compound of Formula (II): Also provided are pharmaceutical compositions comprising a compound of Formula (I) or (II) and methods of using such compounds for treating proliferative diseases.

The invention relates to a method for making a pet food attractant, which takes duck liver and marine fish as a main material, wherein the addition of the duck liver is 50-100%. The method comprises the following steps: mincing the raw material by a mincer, adding a proper amount of water for disinfection, adding protease for enzymatic hydrolysis, adding amino acid and carbohydrate for carrying out maillard reaction after the enzymatic hydrolysis reaction is finished, spray drying to obtain the food attractant specially used for pet, wherein the water content of the finished product is 6-10%.According to the enzymatic hydrolysis method in the invention, the partial protein is degraded to a polypeptide substance which is easy to be absorbd by pet, The specific local flavor food attractant is prepared by controlling the maillard reaction condition and the food attractant product is finally prepared, the food attractant with dark red color has rich meat fragrance, thereby the initiative for ingestion of pet can be enhanced for first time. The food attractant is capable of applying to exploitation of various pet principal food and snacks products.

The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof.

This invention relates, e.g., to a composition that, at room temperature, when contacted with a sample comprising phosphoproteins, can fix and stabilize cellular phosphoproteins, preserve cellular morphology, and allow the sample to be frozen to generate a cryostat frozen section suitable for molecular analysis. The composition comprises (1) a fixative that is effective to fix the phosphoproteins, and that has a sufficient water content to be soluble for a stabilizer and / or a permeability enhancing agent); (2) a stabilizer, comprising (a) a kinase inhibitor and (b) a phosphatase inhibitor and, optionally, (c) a protease (e.g., proteinase) inhibitor; and (3) a permeability enhancing agent (e.g. PEG). Methods are described for preserving phosphoproteins, using such a composition. Also described are endogenous surrogate markers for monitoring protein degradation, including the loss of posttranslational modifications (such as phosphorylation), e.g. the following removal of a cell or tissue from a subject; and exogenous molecular sentinels (e.g. phosphoproteins attached to magnetic nanoparticles) that allow one to evaluate the processing history of a cellular or tissue population sample.

A process for the producing edible protein-containing meal for human and animal consumption and high quality food grade oils from oil seed using iodotrifluoromathane as the solvent is shown. The meal has a significantly improved level of dietary available (absorbable) protein. The process involves the preparation of protein isolates by a procedure which is conducted at room temperature, thus decreases protein degradation and denaturing which is caused by elevated temperatures. The process also provides for extraction of substantially all oils and fats, which interfere with the formation of the protein micelle, from the protein meal providing a cleaner, purer product with high levels of absorbable protein. Such protein isolates can then be used as such or added to formulated foods in order to increase the total protein content of that food. The protein produced and the oils recovered have compositions which are also unique and unobtainable by prior processing methods.

Restenosis of blood vessels after angioplasty is achieved by preventing of cell proliferation, particularly of smooth muscle cells, in blood vessel walls by inhibiting the ubiquitin-proteasome protein degradation pathway. The inhibition is accomplished by administering to the cells in the blood vessel walls a compound, e.g., a protein or small molecule, capable of inhibiting the ubiquitin-proteasome protein degradation pathway. The inhibiting compound is preferably administered by coating the compound on a stent and implanting the stent in the blood vessel after angioplasty.

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 discloses fast alcoholized dark green tea and a preparation method of the dark green tea. The preparation method comprises the following steps of: converting catechin with bitter taste in the raw dark green tea into theaflavin, thearubigin and theabrownin, degrading cellulose into glucose with sweet taste, converting insoluble pectin into soluble pectin (to increase the thickness of a tea soup), and degrading protein into amino acids with umami taste by adding microorganisms and an enzyme solution into the raw dark green tea under the condition with certain temperature and humidity, and applying chemical action to the resulting product in supplementation, and at last neutralizing partial acidic components with baking soda. The technical problems of long fermentation time and the generation of nauseating and sour smells in dark green tea pile fermentation are solved; the tea made from the dark green tea obtained by the preparation method disclosed by the invention is delicate and mellow in taste, orange red and transparent in tea soup, and rich in stale flavor; and the dark green tea is pretty high in contents such as soluble sugar, theaflavin, thearubigin and amino acid, and can reach the taste effect of old tea more than 5 years in about 4 days.

The invention relates to a method for producing functional fertilizers by comprehensive utilization of shrimp and crab shells. The functional fertilizers are produced by utilizing waste of the shrimp and crab shells and have very good disease-resistant and yield-increasing effects to plants. The method is characterized in that calcium carbonate contained in the shrimp and crab shells is changed into water-soluble calcium, the contained protein is degraded into polypeptide or amino acid, important nutritional components needed by the plants and chitosan form a liquid fertilizer rich in nutrition, and the liquid fertilizer can be used for being sprayed on leaves or being flushed on roots. The method has the advantages that no waste water is discharged, the environment-friendly effect is achieved and simultaneously the fertilizer efficiency of the obtained fertilizer is obviously improved.

The present invention relates to a compound represented by a formula (I), antitumor applications and intermediates thereof, and applications of the intermediates, wherein the intermediates are compounds represented by a formula (III) and a formula (IV), the compound represented by the formula (I) has degradation effects on specific target proteins, and mainly comprises three parts, the first partis small molecules binding protein (SMBP), the second part is a link unit (Linker), the third part ubiquitin ligase binding moiety (ULM) is a ligand with ubiquitination function, SMBP and LIN are covalently bound, and LIN is covalently bound to ULM. According to the present invention, a series of the designed and synthesized compounds of the present disclosure have wide pharmacological activities,have function of degradation of specific proteins and / or inhibition of activities, and can be used for related tumor treatment.

The present invention provides compounds, compositions thereof, and methods of using the same for the targeted degradation of proteins, and the treatment of target protein-mediated disorders.

An additive of flue-cured tobacco is prepared from the protein degradation enzyme, starch degradation enzyme, pectin degradation enzyme, poly-phenol oxidase, cellulose, VC and potassium tartrate through adding them to water, stirring for dissolving and filtering to obtain the liquid product. It can be sprayed onto the leaves of tobacco to decreasing the content of organic high-molecular substances in tobacco leaf and improving its quality.

The invention provides a green production method of chilled fillets. The method mainly comprises the following steps: preparing raw material fish, temporarily cultivating fish in cold water, performing movement bloodletting in cold water, preprocessing (removing scales, heads, tails and internal organs), cleaning with cold water, cutting into slices, removing fish bones and repairing, grading, sterilizing with electrolyzed ozone water, dewatering, spraying for coating, drying the water on the surface of fish, sterilizing with ultraviolet, performing atmosphere packaging and transporting. The main characteristics of the method of the invention are as follows: 1) electrolyzed ozone water and ultraviolet are used to sterilize the fillets and reduce the initial microbial content of raw material, chlorine dioxide and preservative are not used so as to ensure that the production technology is green and environmentally friendly; 2) temporarily cultivating in cold water, low-temperature movement bloodletting and whole-process low temperature operation are adopted to effectively control the microbial spoilage of the chilled fillets, reduce fat oxidation and protein degradation and ensure the freshness of the product; and 3) the green composite film preservative is coated on the chilled and sterilized fillets, thus effectively prolonging the shelf life of the chilled fillets.

The invention discloses an extracting method of oyster peptides. The extracting method comprises the following steps: homogenizing after viscera is removed from oyster meat, firstly adding active dryyeasts and arabinose for deodorization, then adding beta-cyclodextrin for treatment, adding complex proteases for constant-temperature enzymatic hydrolysis after a pH value of a deodorized oyster meathomogenate is regulated, performing enzyme inactivation after the end of enzymatic hydrolysis, filtering centrifugal supernatant, freezing and drying to obtain the oyster peptides. The extracting method disclosed by the invention has the benefits that the extracting method has the advantages of being low in input, simple to operate, good in protein degradation effect, high in oyster peptide yield, high in sensory acceptance and easy for industrialized scale production; the molecular weights of the obtained oyster peptides are uniformly distributed, and the content of the oyster peptides withmolecular weights ranging from 4000 to 6000 is more than 87 percent, therefore, application values and market potentials are good.

The preparation of oyster oral liquid includes the following steps: homogenating oyster with water, hydrolysis with papaya proteinase to eliminate fishy smell of the protein; enzymolysis of oyster pulp and sugar and heat treatment to further eliminate fishy smell of alkali matter; and further acid and heat treatment for eliminating fishy smell of alkali matter. Through the said process, osyter pulp for compounding oyster oral liquid is produced. The heat treatment can promote the interaction of sugar, organic acid and fishy smell matter and the volatilization of fishy smell matter. The present invention eliminates fishy smell of oyster by means of enzymolysis, chemical and physical treatment and increases the storing stability of oral liquid via protein degradation.

The invention relates to a drug with autophagia inductivity for treating the diseases caused by the accumulation of misfolded proteins and a screening method thereof. Quantitative analysis is carried out to the changes of the fluorescence marked LC3 in the cells of the known medicine combination and to the changes of the fluorescence marked FYVE in the cells to obtain the candidate compound of an autophagia inductive agent; and then longevous protein degradation and polyQ degradation is carried out to finally determine the drug with the autophagia inductivity for treating the diseases caused by the accumulation of misfolded proteins. The method of the invention is a simple and high effective compound screening method which can affect autophagia.

The invention relates to a new bifunctional small molecule, a preparation method of pharmaceutically acceptable salt thereof, hydrate or prodrug and application of the compounds and medicinal compositions in treating diseases such as tumor, inflammation and immune diseases. The bifunctional small molecule provided by the invention is a protein degradation targeted combo (PROTACs) which can selectively induce BET protein degradation. According to the invention, a BET protein small molecular inhibitor is connected with a von Rippel-Lindau (VHL) protein ligand in E3 ubiquitin ligase complex by a connecting arm to obtain the bifunctional small molecule.

Provided is a system which can induce the degradation of a protein of interest in a mammalian cell system reliably and stably within a short time. A mammalian cell inducible for protein degradation, the degradation of a protein of interest being induced by an auxin, in which the mammalian cell has both a TIR1 family protein gene from rice and a chimeric gene expressing a protein of interest labeled with a plant Aux / IAA family protein.

The invention belongs to the technical field of microorganisms, and particularly relates to decomposition promoting and nitrogen promoting microbial inoculum for composting of excrement and urine of livestock and poultry and a preparation and application method. The decomposition promoting and nitrogen promoting microbial inoculum adopts the technical scheme that the decomposition promoting and nitrogen promoting microbial inoculum is bacillus brevis, the decomposition promoting and nitrogen promoting microbial inoculum is preserved in China General Microbiological Culture Collection Center at27 March, 2020, and the preservation No. is CGMCC No.19516. A microorganism composition prepared from the bacillus brevis comprises protein degradation bacteria, cellulose degradation bacteria, directional decomposition promoting microorganisms, keratin degrading bacteria, lactic acid bacillus, ammonia oxidizing bacteria and sulphur-oxidising bacteria. The protein degradation bacteria comprise bacillus subtilis. The microorganism composition can treat livestock and poultry excrement and urine pointedly, the mineralization rate during composting of the livestock and poultry excrement and urinecan be reduced, the humification rate can be increased, volatilization of ammonia and foul gas can be avoided, and the composting product quality can be improved.

The invention relates to methods of treating protein degradation disorders, such cellular proliferative disorders (e.g., cancer) and protein deposition disorders (e.g., neurodegenerative disorders). The invention provides methods and pharmaceutical compositions for treating these diseases using aggresome inhibitors or combinations of aggresome inhibitors and proteasome inhibitors. The invention further relates to methods and pharmaceutical compositions for treating multiple myeloma. New HDAC / TDAC inhibitors and aggresome inhibitors are also provided as well as synthetic methodologies for preparing these compounds.

The invention relates to a novel pyrrolopyridone double-functional molecule, and pharmaceutically acceptable salts, hydrates, prodrug thereof, and a pharmaceutical composition taking the novel pyrrolopyridone double-functional molecule as an active component, and applications of the above compounds and the pharmaceutical composition in treatment or prevention of tumor, inflammation, and immunity diseases. The double-functional molecule is a proteolytic targeting chimera (PROTAC); the preparation method is mature; connecting arms are adopted to connect BET protein small molecular inhibitors andCereblon protein ligand in E3 ubiquitin ligase complex so as to obtain the double-functional molecule; the obtained compound is capable of realizing selective induction of BET protein degradation; and the tumor prevention effect is obvious.

The invention discloses alkaline pectinase PelN, as well as encoded gene and an application of the alkaline pectinase PelN. The PelN is protein formed by an amino acid sequence shown as sequence 1 in a sequence table, and has alkaline pectinase activity, and the preservation number of a recombinant bacterium (escherichia coli) BL21 (DE3) PelN containing the encoded gene of the protein in China General Microbiological Culture Collection Center (CGMCC) is CGMCC No. 7166. Experiments prove that the enzyme activity of the protein PelN for degrading polygalacturonic acid is 4590-4950U / mg; the heat stability is better; the relative enzyme activity is above 90% through heat preservation for 120 minutes at 45 DEG C; the optimum pH value of the alkaline pectinase is 9.8; the optimum temperature is 65 DEG C; and production methods of the protein PelN, the recombinant bacterium and the alkaline pectinase provide efficient paths for industrial large-scale production of the alkaline pectinase.

The invention discloses a rapidly-degraded Cas9-ODC422-461 fusion protein and application thereof, and belongs to the technical field of molecular biology. According to the rapidly-degraded Cas9-ODC422-461 fusion protein and the application, a humanization Cas9 protein is transformed with a genetic engineering method, a PEST protein degradation sequence is added, and therefore the rapidly-degraded Cas9-ODC422-461l fusion protein is obtained. The Cas9-ODC422-461l fusion protein can conduct induced control over an expression of Cas9; the staying time of the Cas9-ODC422-461l fusion protein in cells is shortened; and nonspecific cutting toxicity of Cas9-ODC422-461l overexpression to the cells is accordingly reduced. The rapidly-degraded Cas9-ODC422-461l fusion protein is safer when being used for drug screening or gene modification; and the fusion protein can be further used for gene therapy.