29 results about "Metallo enzyme" patented technology

Provided are compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders, or symptoms thereof mediated by such metalloenzymes. In some embodiments, a provided compound is a compound of Formula I,or a pharmaceutically acceptable salt thereof. In some embodiments, a provided method is a method of alleviating or abating a disorder or disease associated with aldosterone synthase (CYP11B2) or ameliorating a symptom thereof.

The application discloses an emulsion microreactor for cascade reaction and a preparation method and application thereof. The emulsion microreactor is prepared by the following steps: acidolysis of agar, hydrophobic modification, mixing of obtained interface stable modified agar nanoparticles, enzymes and buffer to obtain an aqueous phase; mixing of a substrate, a catalyst and an organic solvent to obtain an oil phase; and mixing of the aqueous phase and the oil phase to obtain the emulsion microreactor. The emulsion microreactor is used for synthesizing 4-biphenylcarboxylic acid ethyl ester by using lipase and a metal palladium catalyst, solves the problem of poor compatibility between the catalyst metal palladium and the lipase, spatially separates the lipase and the metal palladium, improves the cascade catalytic efficiency of the metal enzyme, and finally the yield of the product 4-biphenylcarboxylic acid ethyl ester can reach 55.85%; and the metal enzyme cascade reaction is completed in one pot in the emulsion microreactor, avoids separation of an intermediate product, expands the range of catalytic reactions, and provides a reaction platform for other high-value-added pharmaceutical intermediate products.

The invention discloses an application of a CuN3 / Cu3 artificial metalloenzyme in preparation of a zinc air battery and a self-powered sensing system. The enzyme simulates the active center of multi-copper oxidase, and shows high-performance catalytic activity on oxygen reduction reaction in a chemically favorable environment (half-wave potential E1 / 2 is equal to 0.86 V). The artificial metalloenzyme provided by the invention is verified in zinc air batteries (ZABs) and self-powered sensing systems (SPSSs) as an efficient ORR catalyst, and shows high power density, long-term stability and high sensitivity to a target substance glucose in a complex environment.

The present disclosure provides a method for biocatalytic production of a polycyclic peptide comprising providing a peptide sequence containing a recognition motif for a radical S-adenosylmethionine metallocnzyme (SAM enzyme), exposing the peptide sequence to an enzymatic reaction including catalysis under standard enzymatic reaction conditions with the radical SAM enzyme, and generating a further cyclized peptide by modifying a product of the enzymatic reaction chemically and / or via enzymes. The radical SAM enzyme catalysis generates macrocyclic modifications using unactivated carbon centers. The product of the enzymatic reaction may be modified using haloalkane- or haloacetyl-containing compounds, macrocyclases, or additional radical SAM enzymes. The peptide sequence may be altered at permissive sites to generate libraries of polycyclic peptide structures. The enzymatic reaction may occur at ambient temperature and pH under buffered aqueous conditions.

Provided are a method for preparing a metalloenzyme inhibitor compound 1-cyclopropyl-2-(6-(difluoromethyl)pyridazin-4-yl)-5,6-difluoro-1H-benzo[d]imidazole, and an important intermediate for preparing the compound.

The invention discloses a CuN3 / Cu3 artificial metalloenzyme with precise coordination control and a preparation method of the CuN3 / Cu3 artificial metalloenzyme. The CuN3 / Cu3 artificial metalloenzyme with precise coordination control is reasonably designed by combining an excellent atomic structure and an electron coordination environment of a monatomic catalyst. The enzyme simulates the active center of multi-copper oxidase, and shows high-performance catalytic activity on oxygen reduction reaction in a chemically favorable environment (half-wave potential E1 / 2 is equal to 0.86 V). Advanced characterization and density functional theory calculation are utilized, the synergistic effect of CuN3-Cu3 sites in an enzyme sample mode is systematically studied, it is revealed that the change of the energy level of a d orbit reduces the potential barrier of the reaction, and the coupling interaction between CuN3 monatomic and a Cu3 cluster enhances adsorption and desorption of an oxygen intermediate, so that the reaction kinetics is improved.

The present invention discloses a method for preparing a superabsorbent resin using metalloenzyme catalysis, and relates to the technical field of resin material preparation. The method comprises the following steps: incubating a protein and a metal salt in deionized water at room temperature, adjusting the pH with an alkaline solution, allowing to stand at room temperature, and then centrifuging. Finally, washing with deionized water and drying the resulting metalloenzyme obtains the metalloenzyme; and mixing a resin monomer, a neutralizing solution, a metalloenzyme, acetylacetone, and a crosslinking agent in deionized water, allowing the mixture to stand at room temperature to obtain a resin colloid. Granulation and drying obtain the superabsorbent resin. The present invention utilizes an artificially synthesized metalloenzyme instead of a natural laccase to carry out the polymerization reaction. The metalloenzyme has a low preparation cost, and the amount of metalloenzyme used to oxidize acetylacetone is less than that of the natural laccase. Furthermore, the metalloenzyme-driven free radical polymerization can generate free radicals to complete resin polymerization without requiring external high-temperature stimulation. This method reduces preparation costs without affecting the resin's high water absorption and water retention, thereby achieving green synthesis of superabsorbent resin at room temperature.

The invention belongs to the field of computer-aided drug design, and discloses a metal binding group extraction method based on chemical informatics analysis and modeling. The method comprises the following steps: constructing a metal binding compound data set; training and optimizing a metal combined compound prediction model by using a decision tree-based model and a graph neural network algorithm; using an SHAP interpretable method to analyze a relationship between the key features and a prediction result, and deriving a structure fragment with potential metal binding capacity; according to the attention score of the Attentive FP model, an atomic weight heat map of molecules in the test set is drawn, and key metal binding fragments are determined; molecules in the training set are fragmented, and representative substructures are extracted; a metal binding fragment chemistry library is compiled. According to the method, the problem that metal binding group extraction is limited to a compound structure data set is solved, efficient extraction of any metal ion binding group is realized, and discovery and research of metalloenzyme-related drugs are accelerated.

The present invention provides an intelligent engineered bacterial system, its preparation, and application in anti-tumor drugs. The intelligent engineered bacterial system is a bacterium loaded with a plasmid, which has a tropism for tumor tissue. The plasmid contains a gene fragment encoding a fusion protein, and the fusion protein is secreted and expressed by the bacteria. The fusion protein comprises protein A, an anti-tumor peptide, and a matrix metalloenzyme-2 sensitive peptide that connects the two and can be targeted and cleaved by matrix metalloenzyme-2. The protein A can inactivate the anti-tumor peptide. After inducing the expression of the fusion protein in vitro, the intelligent engineered bacterial system is injected into tumor-bearing mice. Driven by hypoxia and immunosuppression, the bacteria can tend to and colonize the tumor site. The matrix metalloenzyme-2 highly expressed in the tumor site is used to cut off the sensitive peptide, so that the activity of the anti-tumor peptide can be restored and accurately released locally in the tumor, greatly improving the anti-tumor effect of the engineered bacteria.

The pharmaceutical compounds have anti-inflammatory activity and, in some embodiments, can function as metalloenzyme inhibitors for beneficial modulation of metalloproteins. The pharmaceutical compositions can include a therapeutically effective amount of the compound and a pharmaceutically acceptable vehicle. The pharmaceutical compositions can be useful for treating disorders associated with chronic inflammation and / or misregulation of metalloenzymes, including hemochromatosis, cancers such as breast cancer, or neurodegenerative diseases such as Alzheimer's disease.

The invention belongs to the technical field of bacterium detection, and particularly relates to a psychrophilic bacterium detection method, a primer pair, a probe and application. The detection method comprises the following step: carrying out amplification detection by using one or more primer pairs and / or probes in a TY1F and TY1R primer pair and / or probe, a TY2F and TY2R primer pair and / or probe and a TY3F and TY3R primer pair and / or probe. According to the detection method, the psychrophilic bacteria in the sample can be rapidly detected, the species proportion of gram-negative bacteria, pseudomonas and pseudomonas fluorescens which is high in harm and produces alkaline metalloenzyme in the psychrophilic bacteria can be clearly determined, and the condition of the psychrophilic bacteria in the sample (such as raw milk) can be better controlled.

Discovery of the first rare earth-dependent enzyme in methylotrophic M. extorquens AM1 prompted research toward understanding the unique chemistry at play in these systems. This enzyme, an alcohol dehydrogenase (ADH), features a La3+ ion closely associated with redox-active coenzyme pyrroloquinoline quinone (PQQ). AM1 also produces a periplasmic PQQ-binding protein characterized by a Lys residue hydrogen-bonded to PQQ. Accordingly, we prepared K115A-, and K115D-PqqT variants to assess the relevance of this site toward metal binding. Isothermal titration calorimetry experiments, and titrations monitored by UV-vis absorption and emission spectroscopies support that K115D-PqqT binds tightly (Kd=0.6±0.2 μM) to La3+ in the presence of bound PQQ and produces spectral signatures consistent with those of ADH enzymes. Addition of benzyl alcohol to La3+-bound PQQ⊂K115D-PqqT produces spectroscopic changes associated with PQQ reduction, and chemical trapping experiments reveal the production of benzaldehyde, supporting ADH activity.

This application discloses the application of Fe / Mn bimetallic enzymes in the preparation of anti-periodontalgia or teeth whitening agents. The Fe / Mn bimetallic enzyme exhibits excellent photothermal properties and peroxidase-like activity; that is, under photothermal synergy, its POD-like activity can be significantly enhanced, generating more ·OH groups. In antibacterial coating experiments against *Porphyromonas gingivalis* and drug-resistant *Staphylococcus aureus*, Fe / Mn BA, through photothermal synergistic chemokinetic therapy, achieved antibacterial rates exceeding 90%. By treating periodontitis through anti-inflammatory and antibacterial action and achieving teeth whitening through pigment degradation, the application of this biatomic nanozyme provides a new research direction for the application of artificial enzymes in oral diseases and is expected to open up broader pathways to address the challenges currently faced by artificial enzyme antibacterial technologies.

The present invention provides a solid form of a metalloenzyme inhibitor compound 1-cyclopropyl-2-(6-(difluoromethyl)pyridazine-4-yl)-5,6-difluoro-1H-benzo[d]imidazole, and in particular to a crystal form and an amorphous solid form, and a preparation method for the compound, a pharmaceutical composition comprising the compound, and a use of the compound.

This invention discloses a method for improving the soluble expression of the large subunit of [NiFe] hydrogenase in *Escherichia coli*, belonging to the fields of protein engineering and industrial microbiology. This method involves fusing a short-chain solubilizing peptide XXA to the C-terminus of the target [NiFe] hydrogenase large subunit to form a fusion protein. This design significantly promotes the soluble expression of the target protein while preserving the accessibility of the C-terminal hydrolysis site, enabling it to transform from an inclusion body form to a soluble form under anaerobic high-density fermentation conditions. This invention overcomes the long-standing technical bias in the field that C-terminal fusion hinders the maturation and processing of [NiFe] hydrogenase, achieving a balance between solubilizing effect and processing compatibility. It provides a new technical pathway for the recombinant production of complex metalloenzymes and has significant application value in the industrial preparation of hydrogenase, basic enzymology research, and bioenergy.

The present disclosure relates to plant cells, plants, and plant parts comprising a promoter sequence operably linked to a Copper Transporter 1 protein and / or a Nicotianamine Synthase 1 protein. The plant cells, plants, and plant parts optionally further comprise one or more additional heterologous polynucleotides encoding additional promoter sequences operably linked to additional polynucleotide sequences encoding any one or more of an Antioxidant Protein 1 (ATX1) protein, a Heavy Metal ATPase 4 protein, a Heavy Metal ATPase 5 protein, a Heavy Metal ATPase 9 protein, and / or a Yellow Stripe Like 16 protein. The present disclosure also relates to methods for increasing copper resistance and / or accumulation in a plant cell to reduce fungal decomposition in a plant cell, plant, or plant part and to enhance carbon storage.

Pharmaceutical compounds have anti-inflammatory activity and, in some aspects, may function as metalloenzyme inhibitors for the beneficial regulation of metalloproteins. A pharmaceutical composition may include a therapeutically effective amount of the compound(s) and a pharmaceutically acceptable vehicle. The pharmaceutical compositions may be useful for treating a disorder associated with chronic inflammation and / or metalloenzyme misregulation, including hemochromatosis, cancers such as breast cancer, or neurodegenerative diseases such as Alzheimer's disease.

The invention belongs to the technical field of bacterium detection, and particularly relates to a psychrophilic bacterium detection method, a primer pair and application. The detection method comprises the following step: carrying out amplification detection by using one or more of a TY1F primer pair and a TY1R primer pair, a TY2F primer pair and a TY2R primer pair, and a TY3F primer pair and a TY3R primer pair. According to the detection method, the psychrophilic bacteria in the sample can be rapidly detected, the species proportion of gram-negative bacteria, pseudomonas and pseudomonas fluorescens which is high in harm and produces alkaline metalloenzyme in the psychrophilic bacteria can be clearly determined, and the condition of the psychrophilic bacteria in the sample (such as raw milk) can be better controlled.

The invention discloses an emulsion microreactor for cascade reaction as well as a preparation method and application of the emulsion microreactor. The preparation method comprises the following steps: carrying out acidolysis on agar, then carrying out hydrophobic modification, and mixing the obtained interface stable modified agar nanoparticles with enzyme and a buffer solution to obtain a water phase; mixing a substrate, a catalyst and an organic solvent to obtain an oil phase; and uniformly mixing the water phase and the oil phase to obtain the emulsion microreactor. According to the reactor, lipase and a metal palladium catalyst are used for synthesizing ethyl 4-bibenzoate, the problem that the compatibility of the catalyst metal palladium and lipase is poor is solved, lipase and metal palladium are spatially isolated, the metalloenzyme cascade catalytic efficiency is improved, and the yield of the final product ethyl 4-bibenzoate can reach 55.85%; and the metalloenzyme cascade reaction is completed in one pot in the emulsion microreactor, so that the separation of intermediate products is avoided, the catalytic reaction range is expanded, and a reaction platform is provided for other medical intermediate products with high added values.

The invention relates to the technical field of biological medicine, in particular to a biomarker combination, a kit of the biomarker combination and application of the biomarker combination in diagnosis of acute Stanford B-type aortic dissection (ATBAD). The biomarker combination comprises serum amyloid protein A1 (SAA1), serum amyloid protein A2 (SAA2), C-reactive protein (CRP), neutrophil elastinase (ELANE), matrix metalloenzyme 9 (MMP9), nest protein 1 (NID1), mannose binding lectin 2 (LMAN2) and proprotein convertase subtilisin / kexin type 9 (PCSK9), and the biomarker combination can realize high-sensitivity and high-accuracy detection of ATBAD. And the anti-interference capability is excellent.

The present application relates to the technical field of antitumor drugs, and provides a drug delivery system loaded with artificial metalloenzyme and polyphenol compound as well as a preparation method and application thereof.The present application takes metal clusters fixed in a protein cavity as artificial metalloenzyme, takes abundant edible polyphenol compound as a biological active substrate of the artificial metalloenzyme, and simultaneously adopts pH-sensitive liposomes to encapsulate the artificial metalloenzyme and the polyphenol compound.The pH-sensitive liposomes are stable at physiological pH, but are broken in an acidic tumor microenvironment to release the artificial metalloenzyme and the polyphenol compound; the artificial metalloenzyme accelerates oxidation and polymerization of the polyphenol compound in an environment around tumor tissues and in tumor cells to form a hydrogel self-assembly, and the self-assembly can effectively inhibit growth and distant metastasis of an in-situ tumor.

Embodiments include metalloenzymes and methods for conducting a nitrogen migration reaction catalyzed by a metalloenzyme. Embodiments include metalloenzymes including one or more mutations. A method for forming a non-canonical amino acid includes catalyzing a nitrogen migration reaction to form a non-canonical amino acid using an azanyl moiety-containing substrate and a metalloenzyme catalyst.

The present invention belongs to the field of biomedicine and relates to biomimetic metalloenzymes, and in particular refers to a biomimetic metalloenzyme with a polyamide derivative as a core, and its preparation method and application. The present application prepares a nucleic acid-polyamide polymer catalyst with a core-shell structure having targeting, high biosafety and low immunogenicity. In this system, the catalytic active center is protected by a dense outer nucleic acid shell, while the molecular structure and hydrophobic properties determined by the hyperbranched polymer polyamide are utilized to create a highly "pure" catalytic environment inside, avoiding the dilemma of biomimetic enzyme inactivation in a complex system, and also avoiding the hidden danger of metal ion leakage in the body. By utilizing the three-dimensional structure of the material, it can enter the cell autonomously through recognition, avoiding the use of highly toxic cationic transfection agents. Some of the more major problems currently faced by biomimetic metalloenzymes are solved.