107 results about "Enzyme binding" patented technology

The invention discloses an enzyme linked immunosorbent assay kit for detecting a plasticizer in edible oil and application of the enzyme linked immunosorbent assay kit, and belongs to the technical field of enzyme linked immunosorbent assay. The enzyme linked immunosorbent assay kit comprises an elisa plate coated with a plasticizer coupling antigen, a plasticizer standard substance, an enzyme conjugate working solution, a plasticizer specific antibody working solution, a purification tube, a purification reagent, a standard substance diluent, a sample diluent, a substrate solution, a stop solution and a 10 * concentrated washing solution. The standard substance diluent provided by the invention is used for diluting a plasticizer standard substance at different temperatures to obtain a plasticizer standard solution, and the obtained plasticizer standard solution has basically consistent inhibition ratio, so that the stability of the kit is remarkably enhanced; meanwhile, the standard diluent and other components in the kit have a synergistic effect, so that the enzyme linked immunosorbent assay kit has the advantages of good specificity, high sensitivity, good accuracy and high stability when being used for detecting the plasticizer in the edible oil; therefore, the enzyme linked immunosorbent assay kit has a good application prospect in the detection of the plasticizer in the edible oil.

Provided herein are plasma kallikrein binding proteins such as antibodies binding to active plasma kallikrein and methods of using such proteins in treating hereditary angioedema.

The invention relates to a UGT enzyme subtype substrate specificity prediction method and model. On the basis of a directional message passing neural network, graph structure characterization of a small molecule compound and features of specific protein binding sites of UGT enzyme are deeply fused, a bimodal prediction normal form of'molecule + protein binding sites' is designed, a deep learning model is constructed, conversion from compound center prediction to molecule-enzyme binding site comprehensive prediction is achieved, and the prediction accuracy is improved. And accurate classification prediction can be carried out on UGT enzyme substrates and non-substrates.

The invention relates to the technical field of biological medicine, in particular to an mRNA vaccine based on a protein degradation technology. The mRNA vaccine comprises an mRNA system and a lipid nanoparticle. The mRNA system refers to two mRNAs which can respectively encode an antigen-docking module and a recognition module-E3 ubiquitin ligase binding domain, the E3 ubiquitin ligase binding domain recruits an E3 ubiquitin ligase complex, the antigen is ubiquitinated and degraded into a peptide fragment by utilizing specific binding between the recognition module and the docking module, the peptide fragment is recognized by an MHC-I complex, and the E3 ubiquitin ligase binding domain is used for identifying the MHC-I complex. Then, the body immunity is activated, and the anti-tumor effect is realized. Besides, the invention provides a universal mRNA vaccine, that is, theoretically, different diseases can be treated only by replacing antigens in an mRNA system, the research and development time of the vaccine is greatly shortened, the research and development cost is reduced, a new thought is provided for tumor treatment, and the mRNA vaccine has a huge application prospect.

Plasma kallikrein binding proteins and methods of using such proteins are described.

The invention discloses a PROTAC chimera for targeted degradation of an ROR [gamma] t receptor and application of the PROTAC chimera, the structure of the chimera is RW-L-Re, Re is a ligand capable of being combined with E3 ubiquitin ligase, L is a linking group covalently combined with at least one Re and at least one RW, and Rw is a target protein ROR [gamma] t binding ligand and is selected from one of the following structures. A series of PROTAC chimeras capable of degrading an ROR gamma t receptor in a targeted manner are designed and synthesized for the first time, a ternary complex is formed mainly by combining a target protein ligand and an E3 ubiquitin ligase ligand with POI and E3 ligase respectively, and then the POI is labeled with a ubiquitination tag and is further degraded by proteasome. Experimental results prove that the PROTAC chimera designed by the invention has excellent ROR [gamma] t receptor degradation activity, and can be used for preparing related drugs for treating autoimmune diseases or tumors.

The invention discloses a method for detecting Escherichia coli in food by combining Fe3O4 (at) Mo-CDs nano-enzyme with an aptamer, according to the method, near-infrared light response molybdenum-doped carbon dot modified Fe3O4 (at) Mo-CDs nano-enzyme is synthesized through a hydrothermal method, the Fe3O4 (at) Mo-CDs nano-enzyme has excellent NIR enhanced peroxidase activity and magnetism, 3, 3 ', 5, 5'-tetramethyl benzidine is oxidized to generate blue oxidized TMB, and the activity and magnetism of the NIR enhanced peroxidase are improved. After the surface of the Fe3O4 (at) Mo-CDs nano-enzyme is functionalized with an escherichia coli nucleic acid aptamer, the POD-like activity of the Fe3O4 (at) Mo-CDs nano-enzyme is inhibited, when Escherichia coli exists, the Fe3O4 (at) Mo-CDs nano-enzyme can be selectively combined with E.coli, the POD-like activity of the nano-enzyme is further inhibited, when the Fe3O4 (at) Mo-CDs nano-enzyme is used for detecting the E.coli in samples such as fruit juice and cakes, the detection limit is as low as 0.767 CFU / mL, and the Fe3O4 (at) Mo-CDs nano-enzyme has relatively high reliability and accuracy and can be widely applied to detection of E.coli. According to the invention, magnetic targeting separation and visual detection of E.coli are realized.

To provide IRAK degraders and uses thereof.SOLUTION: The present invention provides compounds, compositions thereof, and methods of using the same. The compounds include an IRAK binding moiety capable of binding to IRAK4 and a degradation inducing moiety (DIM). The DIM could be DTM, a ligase binding moiety (LBM) or lysine mimetic. The compounds could be useful as IRAK protein kinase inhibitors and applied to IRAK mediated disorders. Compounds of the present invention, and compositions thereof, are useful as degraders and / or inhibitors of one or more IRAK protein kinases. In some embodiments, a provided compound degrades and / or inhibits IRAK-1 / 2 / 3 / 4.SELECTED DRAWING: None

The invention provides a retrotransposase, which comprises a target DNA binding structural domain containing a zinc finger binding motif, a reverse transcriptase structural domain and an endonuclease structural domain, and can be used for reversely transcribing RNA (Ribonucleic Acid) into DNA. The amino acid sequence of the retrotransposase is shown as any one of SEQ ID No.1 to 6 or SEQ ID No.32 to 43 or SEQ ID No.68 to 71 or has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% and 99% identity with the amino acid sequence of any one of SEQ ID No.1 to 6 or SEQ ID No.32 to 43 or SEQ ID No.68 to 71. The invention also relates to a system for modifying DNA. The system comprises the retrotransposase provided by the invention or a nucleic acid encoding the retrotransposase provided by the invention; and a donor RNA or a nucleic acid encoding the donor RNA, the donor RNA comprising: a sequence that binds to the retrotransposase and a heterologous sequence.

The application discloses a PROTAC compound with RORgamma t receptor targeted degradation and purposes thereof, which is a compound with a structure shown in a general formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutical composition thereof. e is a ligand capable of combining with an E3 ubiquitin ligase; the L is a linking group covalently combining at least one R e and at least one R W ; the R w is a target protein RORgamma t binding ligand; the application is based on the target point of RORgamma t and the PROTAC technology, and a series of RORgamma t-PROTACs are designed and synthesized for the first time. The mechanism is that the target protein ligand and the E3 ubiquitin ligase ligand are combined with POI and E3 ligase respectively, so as to form a ternary complex of "POI-PROTAC-E3 ligase". Then, the POI is marked with a ubiquitination label, and is degraded by a proteasome. The advantages of RORgamma t-PROTACs mainly include targeting of "undruggable proteins", small dosage, low toxicity, and difficulty in drug resistance. W -L-R e (I)

A composition and its uses and additionally a kit are provided. The composition is a synthetic self-complementary oligonucleotide that has a double-stranded region and a loop, wherein the double-stranded region contains a binding sequence for PaqCI. Additionally, the oligonucleotide includes unligatable 3′ and 5′ ends that cannot be cleaved by PaqCI. This oligonucleotide composition has been combined with PaqCI or a variant of PaqCI Type IIS restriction endonuclease in a reaction mixture, where the reaction mixture includes PaqCI or variant that can further be combined with a ligase and optionally a deadenylase, crowding molecule such as PEG and / or a repair enzyme such as Endo MS. The kit includes the oligonucleotide and Type IIS restriction endonuclease in the same or different containers.

The present invention addresses the problem of providing a novel compound having a Cerebron E3 ligase binding ability. It is possible to provide a compound represented by formula (I) [in the formula, each symbol is as set forth in the description], formula (II) [in the formula, each symbol is as set forth in the description], formula (III) [in the formula, each symbol is as set forth in the description], or formula (IV) [in the formula, each symbol is as set forth in the description], or a pharmacologically acceptable salt thereof. # imgabs0 #

The present application relates to a kind of metal-organic framework mediated multi-enzyme nanoparticles and its application, especially the method for alpha-amylase detection. By detecting product absorbance, the quantitative detection of alpha-amylase activity is realized. According to the nature of MFM analog enzyme and its ability as natural enzyme carrier, Agl@MFM@Gox@MFM is prepared, compared with natural enzyme, the composite material has strong resistance, can successfully protect the activity of enzyme. Based on the cascade catalytic system of multi-enzyme nanoparticles Agl@MFM@Gox@MFM, a biosensor is first synthesized and established for detecting alpha-amylase, successfully combines chemical catalyst with natural enzyme, has wide detection linear range (5-500 U / L) while has excellent specificity to alpha-amylase. Benefited from the advantages of low cost, easy preparation and excellent stability, the colorimetric sensor has been successfully used to determine the activity of alpha-amylase in koji.

Provided is a bifunctional compound, or a pharmaceutically acceptable salt, hydrate, solvate, metabolite or prodrug thereof, wherein the bifunctional compound is represented by Formula (I):wherein:ABM is an androgen receptor binding moiety;-L- is a linking moiety; andCLM is a cereblon E3 ubiquitin ligase binding moiety represented by Formula (II)-1:wherein one end of the -L- is covalently joined to Q3, Q4, Q5 or Q6; and the other end of the -L- is covalently joined to the ABM. Also provided are a pharmaceutical composition comprising the bifunctional compound and a method for treating an androgen receptor related disease by administering the bifunctional compound.

Described in several example embodiments herein are engineered bifunctional receptors that can include an E3 ligase binding domain and a target binding domain operatively coupled to the E3 ligase binding domain. In some embodiments, the engineered bifunctional receptors are capable of targeted degradation of a target protein. Also described in several example embodiments herein are compositions, formulations, and cells that can include or generate the engineered bifunctional receptors and uses thereof.

The present disclosure relates to compounds, compositions, and methods for treating diseases or conditions mediated by aberrant histone deacetylase 8 (HDAC8) activity. The compounds disclosed comprise HDAC8 Targeting Ligand TL moiety covalently linked to a Dergon moiety recruiting E3 ubiquitin ligase to HDAC8. In some embodiments, the degron may bind the E3 ligase which is von Rippel-Lindau (VHL) tumor suppressor.

Disclosed is a novel piperidinedione compound of Formula 1 or a pharmaceutically acceptable salt thereof. Uses of the novel piperidinedione compound of Formula 1 or a pharmaceutically acceptable salt thereof as an anti-tumor agent or an immunomodulatory for treatment of CRBN protein-mediated diseases are disclosed. Also the compound or salt thereof can be used an E3 ligase binder in a PROTAC compound comprising a protein of interest ligand, a linker and an E3 ligase binder. Therefore, a PROTAC compound or a pharmaceutically acceptable salt thereof wherein, as an E3 ligase binder, the compound or salt thereof 1 is connected to the linker is disclosed:

A compound of formula I or a stereoisomer, isotopic isomer, tautomer or pharmaceutically acceptable salt thereof: wherein a ligand that binds to Nef protein (NB) is covalently linked to a ligand that binds to E3 ligase cerebron (CB) via a linker (L).

This invention relates to the field of biopharmaceutical technology, and more particularly to a type of beeswax ( Fraxinus pennsylvanica This invention relates to a pollen allergen composition, its preparation method, and its application. It reveals that Chinese ash pollen contains more different allergenic proteins compared to European and American ash pollen. Therefore, using Chinese ash pollen as raw material, the resulting ash pollen allergen composition contains novel allergenic protein components that bind more strongly to the serum of Chinese ash pollen allergy patients, resulting in superior efficacy. This invention utilizes the ash pollen allergen composition to prepare a kit. This kit is highly sensitive, highly specific, and easy to operate. By changing the enzyme conjugate, it can be used for two purposes in one kit, achieving dual functions: detection of ash pollen allergen-specific IgE antibodies (in vitro allergen diagnosis) and quantitative detection of IgG antibodies (evaluation of desensitization therapy efficacy) in allergy patients.

The present application relates to nucleic acid molecules for CRISPR cascade nucleic acid detection system and application, and relates to the field of biological detection. The nucleic acid molecules comprise a polymerase binding leading region with a DNA polymerase binding site, a trigger nuclease cleavage region with a trans-cleavage endonuclease binding cleavage site, and an exonuclease polymerization blocking region with a modified 3' end; after the trigger nuclease cleavage region is cleaved, the polymerase binding leading region and the exonuclease polymerization blocking region are connected, the DNA polymerase bound to the polymerase binding leading region can extend the exonuclease polymerization blocking region from the 5' end to the 3' end, and a target sequence that can be recognized by the reporter sgRNA of the CRISPR reporter system is synthesized. The CRISPR cascade nucleic acid detection system constructed by using the nucleic acid molecules can realize two-stage cyclic amplification reaction, and improve the reporting speed, reporting intensity and reporting sensitivity of the CRISPR reporter system.

The invention discloses a method for catalytically synthesizing a dabigatran intermediate based on immobilized lipase. The method comprises the following steps: firstly, immobilizing optimized CALB lipase with an amino acid sequence as shown in SEQ ID NO: 2 by taking a dimethyl sulfoxide-resistant carrier comprising silanization modified mesoporous SiO2, polyvinylidene fluoride, polymethyl methacrylate and the like as carriers to obtain immobilized lipase, and then, carrying out a reaction on a compound II serving as a substrate in a DMSO organic phase, so as to obtain the immobilized lipase. The immobilized lipase is utilized to catalyze a compound II and a compound III to perform an addition reaction, and a dabigatran key intermediate compound I is efficiently and highly selectively generated; the immobilized carrier adopted by the invention can effectively tolerate a DMSO solvent, is firm in enzyme binding, can be repeatedly used for more than 10 times, has good activity retention, solves the problem that a biocatalyst is easy to inactivate and difficult to recover in a strong polar solvent, has the advantages of high conversion rate, good stereoselectivity, low production cost and environmental protection, and has a good industrial application prospect.

The present invention is a composition for inhibiting PTEN dephosphorylation enzymes, and specifically, the present invention is characterized by presenting a composition in which a CopA3 peptide derived from the small horned dung beetle binds to a PTEN enzyme via a covalent bond, thereby enabling inhibition of PTEN dephosphorylation enzymes.

This application relates to a source-aware activity ranking-based method for screening DPP-IV repressive peptides, comprising: constructing a training dataset containing positive samples and at least three levels of negative samples; extracting multimodal features of peptides, including at least sequence deep semantic embedding features and pocket structure features; explicitly aligning the above features using a cross-attention mechanism to generate fusion features; inputting the fusion features into the classification branch and ranking branch of a decoupled prediction architecture, outputting classification probability and activity ranking score respectively, wherein the ranking branch uses an independent ranking model and is trained based on preference pairs constructed from data within the same assay source; and performing virtual screening output by combining classification probability, activity ranking score, multidimensional confidence judgment, and ADMET safety screening results. This application achieves structurally interpretable characterization of substrate-enzyme binding modes and improves the statistical significance and generalization stability of peptide activity ranking under cross-laboratory batch effects.

The invention relates to a deoxyribozyme binding arm, a kit, a biosensor and a nucleic acid detection method. The deoxyribozyme binding arm is of an annular structure and comprises a catalytic core A sequence of deoxyribozyme, a monomer amplicon recognition region, a sequence of a fragment containing a detection probe and a deoxyribozyme substrate recognition region; wherein the catalytic core part sequence of the deoxyribozyme comprises a part of sequence in any one of 8-17 type deoxyribozyme, E6 type deoxyribozyme or 10-23 type deoxyribozyme. The invention provides a deoxyribozyme binding arm and a multifunctional DNA nano-machine obtained by combining the deoxyribozyme binding arms, which integrate cutting enhanced rolling circle amplification, self-cutting DNAzyme and rolling circle amplification technologies, construct a self-cascade amplification nano-machine, and can perform molecular signal amplification on the existence of a formulated sequence. The system exhibits an increase in cascade reaction efficiency due to the minimization of the number of independent molecular diffusion / collision events.

The invention is applicable to the technical field of hydroxytyrosol preparation, and provides a method for preparing hydroxytyrosol by combining compound enzyme with molecular imprinting adsorption, which comprises the following steps: crushing fresh olive fruits, and collecting olive fruit pulp; putting the olive pulp into an enzymolysis tank, adding cellulose-pectin compound enzyme and citric acid, and performing enzymolysis; transferring the olive pulp subjected to enzymolysis into a microwave extraction tank, adding purified water, carrying out intermittent irradiation extraction, centrifuging after the extraction is completed, collecting supernate, and carrying out vacuum concentration; and adsorbing the concentrated supernate by using a chromatographic column filled with a hydroxytyrosol imprinted polymer, eluting with water and an ethanol solution in sequence, collecting ethanol eluent, and concentrating to obtain extract, namely the high-purity hydroxytyrosol. The problems that an existing fermentation method is low in yield and high in cost are solved. Generation of byproducts is reduced, and the separation and purification process is simplified; green and sustainable hydroxytyrosol industrial production is realized; and the purification period is shortened to be within 5 hours.

Provided herein are plasma kallikrein binding proteins such as antibodies binding to active plasma kallikrein and methods of using such proteins in treating hereditary angioedema.

Plasma kallikrein binding proteins and methods of using such proteins are described.

Provided herein are systems and methods for transposase-mediated insertion of an adapter construct into a target nucleic acid. A composition can include a nucleic acid molecule, comprising a plurality of barcode sequences and a plurality of capture sequences. The composition can further include a plurality of transpososomes coupled to the nucleic acid molecule, wherein each transpososome comprises an active transposase and a plurality of polynucleotides. The plurality of polynucleotides can include: (A) a pair of transposon end recognition sequences that are bound to the active transposase and (B) a polynucleotide comprising a binding sequence that is hybridized to a capture sequence of the plurality of capture sequences of the nucleic acid molecule.

To provide cereblon ligands and bifunctional compounds comprising the ligands.SOLUTION: The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the 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 disclosure. Specifically, the description provides compounds which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein, so that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activity consistent with the degradation / inhibition of targeted polypeptides of nearly any type.SELECTED DRAWING: None

Provided herein are novel Class 2 Type II and Type V CRISPR-Cas RNA-guided endonucleases such as Cas9 and Cas12 endonucleases and systems comprising the same. Methods of making and methods of using the same are also provided. Exemplary methods of use include modifying target DNA and detecting targeted DNA, which can be useful for therapeutic and diagnostic applications. Some diagnostic applications can take advantage of the collateral nuclease activity of the enzyme bound to the target sequence.