74 results about "Protein aggregation" patented technology

Provided herein are certain compounds and imaging agents useful for detecting a disease or condition associated with protein aggregation, compositions thereof, and methods of their use.

Disclosed is a novel class of fusion proteins to recruit the cell's innate chaperone machinery, specifically the Hsp70-mediated system, to specifically reduce TDP-43-mediated protein aggregation and associated protein conformational diseases.

Compounds comprising an amide-linked coumarin scaffold, compositions comprising same, and method of using such compounds and compositions to inhibit tubulin-associated unit (tau) protein aggregation or alpha-synuclein ( α-syn) protein aggregation in a subject having, or at risk for, tau protein aggregation or α-syn protein aggregation, respectively.

The invention relates to methods and materials for use in treating neurodegenerative diseases associated with pathological protein aggregates and provides fusion proteins comprising: (i) a first portion comprising a sequence of a protein which aggregates pathologically in neurodegenerative disease, such as tau protein, and (ii) a second portion comprising a RING-type E3 ubiquitin ligase, a component of a RING-type E3 ubiquitin ligase complex, or a domain of either. These fusion proteins have utility in selectively or preferentially targeting pathogenic protein aggregates for degradation.

The invention discloses a method for sterilizing a vegetable protein beverage, which comprises the following steps of: adding a composite antibacterial microsphere preparation into a vegetable protein beverage to be treated, uniformly mixing, and performing high-density CO2 treatment and magnetic induction electric field sterilization to obtain a vegetable protein beverage finished product, the composite antibacterial microsphere preparation is prepared by taking fucoidan and a gallic acid acylated quercetin-phospholipid conjugate as a substrate and loading lysozyme and hydroxytyrosol. High-density CO2 and a magnetic induction electric field are adopted for synergistic sterilization, so that the structure of a microbial film can be changed, metabolism is disturbed, a good matrix is provided for electric field sterilization, and the sterilization efficiency is further improved through electric breakdown, magnetic field refining of water molecular groups and heat effect; the composite microspheres are sensitive to an electric field, so that lysozyme and hydroxytyrosol can be triggered to be accurately and quickly released under the action of a magnetic induction electric field, stubborn spores can be efficiently killed, and the killing effect is improved by destroying cell wall structures and disulfide bonds of the spores; meanwhile, protein aggregation and flocculation in the beverage can be effectively prevented, and the stability of a beverage system is guaranteed.

The application provides a screening device and method and application of small molecules for inducing or inhibiting protein polymerization, adopts a solid-state quartz nanopore as a core detection device, drives target proteins or complexes of the target proteins and small molecules to pass through a nanoscale pore, records ion current changes caused by each time of perforation event in real time, analyzes peak current and residence time characteristic values of each event, and can identify whether the proteins are in monomer, oligomer, aggregation or LLPS state. Meanwhile, the nanopore sensing is combined with small molecule processing, a mapping relationship between current signal changes and aggregation state regulation is established, and screening of small molecules for inducing or destroying protein aggregation behavior is realized. The technology has multiple advantages of label-free, single molecule, real-time monitoring and adaptation to multiple protein aggregation states, and breaks through the bottleneck of throughput and resolution capacity of existing methods.

Disclosed herein are small molecule drugs that reduce protein aggregation and their methods of use. One aspect of the invention provides for a method reducing aggregate protein abundance in a protein aggregate, the method comprising administering an effective amount of a compound that stably binds a Glial Fibrillary Acidic Protein (GFAP) to a subject, wherein the aggregate protein comprises BSN, SYN1, MAP2, PLEC, RAB10, MAP1A, DCTN, TUBA4A, SPARE, PRKDC, or any combination thereof.

The invention relates to a wet spinning preparation process of protein modified polyacrylonitrile fibers, and relates to the field of wet spinning preparation processes, the wet spinning preparation process comprises the following steps: S1, heating and softening a spinning stock solution, dropwise adding a protein solution, and fully dissolving to obtain a clear and transparent protein modified spinning solution; s2, the protein modified spinning solution is sequentially subjected to filtering, defoaming, spinning, coagulating bath and drafting, and then the protein modified polyacrylonitrile fiber is obtained; the spinning stock solution is an acrylonitrile-methyl acrylate-itaconic acid ternary copolymerized stock solution. The acrylonitrile-methyl acrylate-itaconic acid ternary copolymerized stock solution is adopted as a spinning matrix, the compatibility with natural protein is improved by introducing a polar group, and the protein is uniformly dispersed at a molecular level in cooperation with a mode of dropwise adding the protein solution after heating and softening, so that the protein agglomeration phenomenon is remarkably reduced, and the uniformity of the internal structure of the fiber is improved.

The invention discloses a sequential enzymatic-ionic synergistic soybean protein isolate modification method, which comprises the following steps: dispersing soybean protein isolate in water to prepare a protein solution, adding glutamine transaminase, carrying out heating reaction to inactivate enzyme to obtain an enzyme cross-linked protein solution, adding MgCl2 into the enzyme cross-linked protein solution, and carrying out heating reaction to induce protein aggregation to obtain a modified soybean protein isolate solution; and cooling to room temperature after the reaction is finished. The invention also discloses an application of the soybean protein product obtained by the sequential enzymatic-ionic synergistic soybean protein isolate modification method as a food additive. According to the method, the sensitization of the soybean protein can be remarkably reduced, meanwhile, the unique stomach resistance-intestinal efficient release dynamic characteristic is shown, and the small intestine peptide fragment release amount is promoted to be increased.

The invention belongs to the field of small molecule polypeptides, and particularly relates to a scallop polypeptide with a protein aggregation resisting function and application of the scallop polypeptide. The pure natural scallop polypeptide is extracted, separated and identified by taking scallops as raw materials through the steps of enzymolysis separation, ultrafiltration purification, LC-MS / MS identification and the like, the amino acid sequence of the scallop polypeptide is TMYWTDVSNGQIHR, the molecular formula is C74H110N22O23S, the average relative molecular mass is about 1707.88 Da, the theoretical isoelectric point is pH = 6.41, and the scallop polypeptide is hydrophilic polypeptide. The scallop polypeptide has the functions of oxidation resistance, protein aggregation resistance and neuroprotection, can be further applied to development of products such as food, medicines and health care products, and has a wide application prospect.

The embodiment of the invention discloses a composite freeze-drying protective agent based on CRISPR-Cas13a, a microsphere molecular diagnostic reagent and a preparation method. The composite freeze-drying protective agent comprises a vitrification matrix component, a structure support component, a protein aggregation inhibitor and a surfactant, the vitrification matrix component comprises mannitol and trehalose, and the mass ratio of mannitol to trehalose is (3-7): (3-7); the structural support component comprises any one of PEG8000, PEG6000 and PEG4000 and any one of glucan 10000, glucan 8000 and glucan 20000, and the mass ratio of the PEG8000 to the PEG6000 to the glucan 8000 to the glucan 20000 is (1-5): (1-5); the protein aggregation inhibitor is bovine serum albumin, and the surfactant is polyoxyethylene sorbitan monolaurate; the mass ratio of the structure supporting component to the vitrification matrix component is (1-5): (3-7), the mass ratio of the protein inhibitor to the structure supporting component is (0.01-1): (2-10), and the mass ratio of the surfactant to the structure supporting component is (0.001-0.1): (2-10).

The present invention relates to a method and system (140) for determining the presence and / or quantity of protein aggregates in a liquid sample comprising a protein. The method comprises: a) measuring ultraviolet-visible spectroscopy (UV- Vis) absorbance of the sample to obtain a UV-Vis absorbance measurement; b) measuring index of refraction (IoR) of the sample to obtain an IoR measurement; c) determining a value for the UV-Vis absorbance measurement; d) determining a value for the IoR measurement; and e) determining the presence and / or quantity of protein aggregates in the sample based on a ratio between the value for the UV-Vis absorbance measurement and the value for the IoR measurement.

The invention discloses a technology for removing viruses from tetanus human immune globulin through a nano film. The process comprises the following steps: pretreating a feed liquid, so that the protein concentration of the feed liquid is 50-60g / L, the pH is 3.8-4.4, and the feed liquid contains 90-110g / L maltose and 50-150mmol / L sodium chloride; then, the feed liquid is subjected to two-stage filtration through a 0.1-micron nylon pre-filtration membrane bag with negative charges and a 20-nm regenerated cellulose (RC) virus removal membrane bag in sequence. According to the process, through optimizing the physical and chemical state of the feed liquid and the synergistic effect of the feed liquid and the functionalized filter membrane, the protein aggregation is effectively inhibited, the membrane pollution is reduced, the virus removal effect is ensured not to be lower than 4log10, the protein load of the RC membrane is remarkably improved to be more than 200L / m, and the product purity is more than or equal to 98%. The invention solves the technical problems of low flux and easy blockage of high-concentration immune globulin in small-aperture virus removal filtration, and is suitable for efficient, safe and large-scale production of blood products.

The invention discloses edible fresh-keeping gel beads for a vegetable protein beverage and a preparation method of the edible fresh-keeping gel beads, and belongs to the technical field of functional food and intelligent packaging. According to the edible fresh-keeping gel beads prepared by the preparation method disclosed by the invention, Schiff base formed by perillaldehyde-yeast protein is used as a liquid core, and Ca < 2 + > is used for pre-crosslinking; the wall material is a sodium alginate-rice protein composite network and can intelligently respond to imine bond protonation caused by pH drop in the beverage storage process, so that controllable release of perillaldehyde is realized, protein aggregation and microbial growth are inhibited, and a clean label and original sense are kept. According to the invention, triple advantages of edible, intelligent response and low cost are taken into consideration, and a plug-and-play fresh-keeping solution is provided for the plant-based protein beverage.

The invention relates to a method for assessing the aggregation propensity of expressed proteins comprising: expressing a protein of interest having a binding tag that upon binding to a detector moiet

Stabilized protein formulations and methods of using them are disclosed herein. In some embodiments, the formulations comprise a protein (e.g., insulin, glucagon, GLP-1 analogs, monoclonal antibodies) and a polyzwitterion, or a pharmaceutically acceptable salt thereof. The disclosed formulations promote delayed and reduced amounts of protein aggregation and subsequent protein fibrillation compared to formulations without polyzwitterions. These more stable formulations retain their potency for a longer period of time even at elevated temperatures.

The application discloses a derivative with a high isoflavone-O-alkylamine structure and application thereof, and a structure formula of the derivative is shown in the following formula: the derivative can be used as an acetylcholinesterase inhibitor and a beta-amyloid protein aggregation inhibitor to treat Alzheimer's disease and other nervous system diseases.

The present invention provides compositions used for the treatment and / or prevention of protein aggregation disorders. [Solution] Proteopathy encompasses a wide range of ailments, including neurodegenerative diseases (e.g., polyglutamine diseases such as huntingtin in Alzheimer's disease, Parkinson's disease, and Huntington's disease, and prion diseases); amyloidosis of other non-neuronal proteins (especially I1-antitrypsin, immunoglobulin light and heavy chains, lactadherin, apolipoprotein, gelzolin, lysozyme, fibrinogen, atrial natriuretic factor, keratin, lactoferrin, and β-2 microglobulin, etc.); sickle cell disease; cataracts; cystic fibrosis; retinitis pigmentosa; and nephrogenic diabetes insipidus. Administration of sulfatase inhibitors is generally suitable for treating and / or preventing protein toxicity associated with proteopathy. Therefore, the present invention provides compositions comprising sulfatase inhibitors for the treatment of proteopathy.

The present invention relates to a buffered protein containing formulation comprising as stabilizing ingredient an amphiphilic surfactant. Said surfactant is formed by polyalkoxylating an a-tocopherol compound. The polyalkoxy residue is either a block copolymer or a statistical or random copolymer composed of a majority of ethylene oxide moieties and a smaller amount of propylene oxide and / or butylene oxide moieties. Said surfactant significantly improves stability, in particular aggregation stability of the protein formulation, while showing low hemolytic activity and good water solubility. Said surfactant is particularly suitable for preparing stabilized formulations of enzymes and immunoglobulin molecules as well as adducts and conjugates comprising such biomolecules. Said formulations may be provided in liquid or dry form and are suitable for the preparation of pharmaceutical compositions. According to another aspect of the invention the use of such formulations in medicine, in particular for diagnostic and / or therapeutic applications is provided. The present invention also relates to a method of preparing such formulations as well as a method for preparing such specific amphiphilic surfactants. According to a further aspect a method for preventing or suppressing protein aggregation of a liquid protein containing formulation in vitro by using an amphiphilic surfactant of the present invention as a stabilizer is provided. A prefilled syringe, comprising a reservoir prefilled with an amount of a formulation of the invention constitutes another aspect of the invention.

The invention belongs to the technical field of protein aggregation detection fluorescent probes, and particularly relates to a protein aggregation detection fluorescent probe containing quaternary ammonium salt and an aggregation-induced emission skeleton as well as a preparation method and application of the protein aggregation detection fluorescent probe. The probe takes a reaction product of 4-bromo-1, 8-naphthalic anhydride and 4-(diphenylamino) phenylboronic acid as the aggregation-induced emission skeleton, and the reaction product is reacted with N, N-dimethylformamide to obtain the protein aggregation detection fluorescent probe containing quaternary ammonium salt and the aggregation-induced emission skeleton. The quaternary ammonium salt group is introduced by sequentially reacting N, N-dimethyl ethylenediamine and diethyleneglycol-2-bromoethyl methyl ether, the quaternary ammonium salt group has the characteristics of water solubility and aggregation-induced emission, and the chemical structure of the quaternary ammonium salt group comprises a naphthalimide mother nucleus, a diphenylamino substituent group and a quaternized side chain.

The invention provides a method for preparing myofibrillar protein gel based on low-temperature sol agar. The method comprises the following steps: preparing myofibrillar protein; dispersing low-temperature sol agar in a sodium chloride solution, and melting to obtain a low-temperature sol agar solution; adding the low-temperature sol agar solution into the myofibrillar protein to obtain mixed sol; centrifuging the mixed sol to remove bubbles; putting the bubble-removed mixed sol into a water bath, and cooking to form heat-conducting gel; and refrigerating the gel at low temperature overnight to obtain the myofibrillar protein gel. According to the method, low-temperature sol agar is dissolved in myofibrillar protein, so that the cooking loss of the pork myofibrillar protein gel is reduced and the aggregation of the myofibrillar protein is promoted at the temperature of 60-80 DEG C, actin of the myofibrillar protein can be protected at the temperature of 78-80 DEG C and is not degraded due to the influence of temperature, and meanwhile, the nutritional characteristics and the gel strength of the pork myofibrillar protein gel are not changed.

Provided is a protein folding agent containing a compound (A) represented by general formula (A). In general formula (A), R1 to R6 are each independently a C1-24 aliphatic hydrocarbon group. Y1and Y2each independently represent a C1-6 aliphatic hydrocarbon group. Moreover, n is an integer of 1 or greater, and Xn- is an n-valent anion. Also provided is a protein folding composition containing the compound (A) and a protein aggregation inhibitor. Furthermore, also provided is a protein folding method including a step (a) for incubating a protein in the presence of the protein folding agent.

A method of detecting the presence of alpha-synuclein aggregation in a biological sample is provided whereby a biological sample is mixed with a reaction sample comprising a population of beads, a fluorophore adapted to bind to protein aggregates and to increase fluorescence when bound to protein aggregates, and alpha-synuclein or a fragment or variant thereof to form a reaction mixture, wherein a significant increase in the fluorescence of the reaction mixture during incubation is indicative of the presence of aggregates of alpha-synuclein in the biological sample.

The invention discloses a derivative with a benzo-nitrogen heterocyclic structure and application thereof, and relates to the technical field of new drug development, and the structure of the derivative is shown as a general formula (I). The compound can inhibit beta-amyloid protein aggregation and acetylcholin esterase activity at the same time, also has excellent antioxidant and neuroprotective effects, and is mainly used for treating and preventing Alzheimer's disease and other nervous system diseases. (I).

The invention discloses an anti-freezing and anti-oxidation compound agent for delaying quality deterioration of rinsing-reduced minced fillet in frozen storage and application of the anti-freezing and anti-oxidation compound agent, and belongs to the technical field of aquatic product processing. The invention relates to an anti-freezing and anti-oxidation compound agent for delaying quality deterioration of rinsing-reduced minced fillet in frozen storage. The anti-freezing and anti-oxidation compound agent comprises the following components in percentage by mass; the components comprise 30-40% of arabinogalactan, 0.005-0.01% of tea polyphenol and the balance of water; when in use, the arabinogalactan is dissolved in water, and the tea polyphenol is added after high-speed shearing treatment. The compound agent can reduce freezing denaturation caused by ice crystal formation and protein aggregation in the freezing storage period of rinsed surimi, reduce surimi quality deterioration caused by fat and protein oxidation, and effectively prolong the shelf life of the surimi.

An object of the present invention is to provide a drug that exhibits an action of inhibiting aggregation of a causative protein of an HRE-associated neurodegenerative disease such as ALS.SOLUTION: Rifampicins selected from the group consisting of rifampicin, derivatives thereof, and salts thereof and / or resveratrols selected from the group consisting of resveratrol and derivatives thereof serve as an active ingredient of a prophylactic or therapeutic drug for a neurodegenerative disease caused by TDP-43 accumulation, or a prophylactic or therapeutic drug for ALS.SELECTED DRAWING: None

Provided is a fusion construct that includes (1) a glycan-targeting domain capable of specifically binding a pre-determined sugar molecule (such as one over-expressed on certain cancer cell surface), (2) an aggregating domain capable of self-aggregation to form multimers among molecules containing the same domain, and (3) an optional solubilizing domain, which is connected to (1) or (2) via a peptide linker optionally containing a protease (such as one over-expressed on certain cancer cell surface) cleavage site. Also provided is using of said construct in treatment of cancer.

The invention belongs to the crossing field of plant-based food and nanotechnology, and particularly relates to a vitamin E-coffee nanoparticle compound as well as a preparation method and application thereof, the vitamin E-coffee nanoparticle compound comprises coffee nanoparticles and vitamin E loaded on the surfaces of the coffee nanoparticles; wherein the coffee nanoparticles are nanoscale particles separated from a coffee extracting solution, and the coffee nanoparticles naturally carry polyphenol compounds; the vitamin E is loaded on the surfaces of the coffee nanoparticles through non-covalent acting force. The vitamin E-coffee nanoparticle compound is used for replacing a traditional coffee polyphenol extract, so that the problems of protein aggregation, precipitation and phase separation caused by interaction of free phenolic acid and vegetable protein are effectively avoided, and the product can be kept in a uniform colloidal state for a long time in the storage period. Meanwhile, the dispersity and the stability of the fat-soluble vitamin E in a water-phase system are greatly improved, and coffee polyphenol carried by the fat-soluble vitamin E is also retained.

Provided herein are certain compounds and imaging agents useful for detecting a disease or condition associated with protein aggregation, compositions thereof, and methods of their use.