46 results about "Epoxide Hydrolases" patented technology

The invention relates to the technical field of bioengineering and fine chemical engineering, in particular to epoxide hydrolase, a gene, a carrier, engineering bacteria and application, and the amino acid sequence of the epoxide hydrolase is shown as SEQ ID NO.3. The epoxide hydrolase disclosed by the invention has the advantages that the epoxide hydrolase is Sphingopyis macrogoltabia EY-1, and the structural formula of the epoxide hydrolase is as shown in the specification. According to the invention, a recombinant plasmid pET-28a-smh containing an optimized gene and a genetic engineering bacterium E.coli / smh are constructed, the engineering bacterium is induced to over-express the recombinant epoxide hydrolase SmEH, and the recombinant epoxide hydrolase SmEH has catalytic activity. According to the present invention, the E.coli / smh whole cell is adopted to respectively catalyze the hydrolysis reaction of the (R)-styrene oxide (SO) and the (S)-styrene oxide (SO) so as to obtain the (R)-styrene oxide (SO) and the (S)-1, 2-phenyl glycol (1-Phenyl-1, 2-ethanediol, PED) with high optical purity, and the application of the E.coli / smh whole cell to respectively catalyze the hydrolysis reaction of the (R)-styrene oxide (SO) and the (S)-1, 2-phenyl glycol (1-Phenyl-1, 2-ethanediol, PED) is provided;

A first aspect of the invention relates to a method of treating or preventing tissue damage, or treating or preventing tissue destruction, in a subject, said method comprising administering to the subject a therapeutically or prophylactically effective amount of a soluble epoxide hydrolase (sEH) inhibitor. A further aspect of the invention relates to a method of treating or preventing leishmaniasis in a subject, said method comprising administering to the subject a therapeutically or prophylactically effective amount of a soluble epoxide hydrolase inhibitor.

Compounds (I) are provided, where R1 and R2 are H or (C1-C3)-alkyl; X is a linear methylene chain of formula —[CH2]n— with n=0, 1 or 2, or a biradical from a branched saturated (C2-C4)-alkylene chain; and A is either a C-radical from a non-aromatic polycyclic 6- to 15-membered carbocyclic ring system, or a C-radical from a polycyclic 6- to 15-membered heterocyclic ring system having one or two O, S or N; wherein the C-radicals are unsubstituted or substituted. Compounds (I) are simultaneously inhibitors of soluble epoxide hydrolase and inhibitors of glutaminyl cyclase. Besides, they reduce the levels of pro-inflammatory cytokines in LPS stimulated BV2 cells, display low cytotoxicity, and have good BBB permeability. Thus, they are useful as multitarget compounds for the prevention or treatment of Alzheimer's disease.

The invention discloses application of heart washing soup in preparation of a medicine for reducing soluble epoxide hydrolase in liver. The heart washing decoction disclosed by the invention can regulate and control soluble epoxide hydrolase and 14, 15-epoxy eicosatrienoic acid, and can improve central neuron insulin resistance, so that diabetes mellitus can be treated, and symptoms of Alzheimer disease can be improved.

The present invention discloses the construction and application of a recombinant Gluconobacter oxydans, belonging to the fields of genetic engineering and whole-cell catalysis. The present invention heterologously expresses an epoxide hydrolase from Sphingomonas in Gluconobacter oxydans, and simultaneously utilizes the alcohol and aldehyde dehydrogenases bound to the membrane of Gluconobacter oxydans itself to synthesize R-mandelic acid in a one-step process using styrene oxide as a substrate. The present invention combines the transcriptome data of Gluconobacter oxydans, screens 7 strong promoters using green fluorescent protein as a reporter gene, and determines the strongest promoter P for expressing the epoxide hydrolase gene. 12780 , ultimately significantly increasing the yield of R-mandelic acid.

The invention belongs to the technical field of medicinal chemistry, and discloses a modular preparation method and application of a protein degradation agent targeting soluble epoxide hydrolase (sEH). The derivative has a structural general formula as shown in a formula (I), wherein X and Y substituent groups can be randomly combined. The compound can effectively degrade sEH level in cells and living bodies, and shows a remarkable protective effect on acute liver inflammation of mice in the living bodies. Particularly, the compound shows excellent degradation activity (EC50 = 2.9 nM) in 1d, can quickly relieve acute inflammation induced by LPS, and can be used for research and development of drugs for acute inflammation related diseases.

The present application relates to an aromatic-substituted benzimidazole compound, a cis-trans isomer, a hydrate, a solvate, a pharmaceutically acceptable salt or a prodrug thereof. The present application also relates to a method for preparing an aromatic-substituted benzimidazole compound, and the use of the aromatic-substituted benzimidazole compound as a soluble epoxide hydrolase inhibitor. The aromatic-substituted benzimidazole compounds described herein exhibit extremely high inhibitory activity against soluble epoxide hydrolase, with IC 50 values in the nanomolar range or even lower.

The present invention relates to the technical field of compound synthesis, and more specifically, to a compound containing benzothiazole or benzoxazole, a preparation method thereof, and an application thereof. The structural formula of the compound containing benzothiazole or benzoxazole is as follows: wherein Y represents O or S, X represents hydrogen or halogen, and R represents any one of a substituted or unsubstituted C3-C8 cycloalkyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted C1-C10 alkyl, and a substituted or unsubstituted C3-C10 alkenyl. The compound can be used as a soluble epoxide hydrolase inhibitor, thereby having a certain therapeutic effect on diseases caused by soluble epoxide hydrolase disorders.

Provided herein are methods of preventing, suppressing, or treating cancer cachexia in a subject as well as methods of prolonging survival of a subject in need of cancer cachexia treatment. Such methods include administering an inhibitor of soluble epoxide hydrolase (sEH).

Described herein are novel piperidine urea derivative compounds and pharmaceutical compositions thereof for the treatment of neurodegenerative disorders and diseases mediated by soluble epoxide hydrolases.

The present application relates to PET imaging of soluble epoxide hydrolase (sEH) 18 F-FNDP. Disclosed herein are radiofluorinated FNDPs for PET imaging of soluble epoxide hydrolase (sEH) and methods of use thereof, in particular, compounds of Formula (I) of the present application and uses thereof are disclosed.

This invention provides a berberine derivative, a pharmaceutical composition, and its application, relating to the field of medicinal chemistry. The main skeleton of the berberine derivative is berberine with a urea group. By connecting different substituents to different sites on the berberine skeleton through the urea group and changing the oxidation state of the C ring, a series of berberine derivatives with high activity against soluble epoxide hydrolase were obtained. The IC50 value of the berberine derivatives inhibiting soluble epoxide hydrolase reaches the nanomolar level, indicating that the berberine derivatives have a highly efficient inhibitory effect on soluble epoxide hydrolase. Thus, by inhibiting soluble epoxide hydrolase, an anti-inflammatory effect can be achieved, which has good application scenarios.

The invention discloses application of epoxy hydrolase derived from rhodosporidium toruloides in asymmetric synthesis of epoxide intermediates, and belongs to the technical field of bioengineering. According to the method, firstly, recombinant bacteria E.coli / Rteh for expressing epoxy hydrolase derived from rhodosporidium toruloides are used as a whole-cell catalyst, and characterization analysis is carried out on 12 substrates, so that the enzyme has catalytic activity on various epoxides. The (R)-tebuconazole epoxy intermediate with high enantiomer purity (ee = 76.8%) can be obtained in the chiral resolution reaction of the E.coli / Rteh whole-cell catalysis racemization tebuconazole epoxy intermediate, and the yield is 33.1%. The method has the advantages of mild reaction conditions, environmental friendliness, high catalytic activity, high optical purity of the product and the like, and has important application prospects.

Compounds (I) are provided, wherein R1 and R2 are H or (C1-C3)-alkyl; x is a linear methylene chain of formula-[CH2] n-, n = 0, 1 or 2, or is a divalent group of a branched saturated (C2-C4)-alkylene chain; and A is a C-group from a non-aromatic polycyclic 6 to 15 membered carbocyclic system, or a C-group from a polycyclic 6 to 15 membered heterocyclic system having one or two of O, S or N; wherein the C-group is unsubstituted or substituted. Compound (I) is both an inhibitor of soluble epoxide hydrolase and an inhibitor of glutaminyl cyclase. In addition, compound (I) reduces the level of pro-inflammatory cytokines in LPS-stimulated BV2 cells, shows low cytotoxicity and has good BBB permeability. Therefore, they are useful as multi-target compounds for the prevention or treatment of Alzheimer's disease.

The present disclosure provides a recombinant host system for producing 9,10,16-trihydroxyhexadecanoic acid (aleuritic acid), wherein the host system is transformed with: (i) a first recombinant expression vector comprising nucleic acid sequences encoding the desaturase enzyme and the epoxygenase enzyme, and a second recombinant expression vector comprising nucleic acid sequences encoding the epoxide hydrolase enzyme and the monooxygenase enzyme, or (ii) a first recombinant expression vector comprising nucleic acid sequences encoding the desaturase enzyme and the bifunctional epoxygenase hydrolase enzyme, and a second recombinant expression vector comprising a nucleic acid sequence encoding the monooxygenase enzyme. The present disclosure further provides methods for producing aleuritic acid using the recombinant host system.

This invention discloses a method for preparing 1,2-pentanediol, comprising using 2-pentanone as a substrate, adding 2-keto reductase, linalool dehydratase, formate dehydrogenase, lysozyme, coenzyme NAD+, and water to react and obtain n-pentene. The obtained n-pentene is then thoroughly mixed with ethanol. This mixture is then fed into a reaction system containing olefin monooxygenase, epoxide hydrolase, formate dehydrogenase, lysozyme, coenzyme NAD+, MgSO4, and water using a fed-batch method. After the n-pentene and ethanol mixture has been completely added, the reaction continues for a period of time, followed by extraction to obtain 1,2-pentanediol. This preparation method uses 2-pentanone as a raw material, catalyzing the synthesis of 2-pentanol via 2-keto reductase. 2-pentanol is then catalyzed by a dehydrating enzyme to generate n-pentene, which is then catalyzed by an olefin monooxygenase to generate 1,2-epoxypentane. Finally, epoxide hydrolase ring-opens the 1,2-pentanediol. This process requires only four enzymatic catalytic reactions for efficient synthesis.

The application provides a glycyrrhetinic acid derivative, a pharmaceutical composition and application thereof, relates to the technical field of medicinal chemistry, and the main skeleton of the glycyrrhetinic acid derivative prepared by the application is glycyrrhetinic acid with a urea group; the 3th position, the 11th position, the 18th position and the 30th position of the glycyrrhetinic acid are modified, so that the glycyrrhetinic acid derivative has nanomolar level inhibitory activity on soluble epoxide hydrolase. Different urea group substituents are introduced into the 30th position on the basis of 18alpha / 18beta-glycyrrhetinic acid, and the activity difference between different substituents is small, but when different urea group substituents are connected to the 20th position of 18alpha / 18beta-glycyrrhetinic acid, the inhibitory effect of the glycyrrhetinic acid derivative on soluble epoxide hydrolase is greatly reduced. The glycyrrhetinic acid derivative prepared by the application has high inhibitory effect on soluble epoxide hydrolase, so that the inhibitory effect on inflammation can be realized by inhibiting soluble epoxide hydrolase, and the glycyrrhetinic acid derivative has good application prospect.

The invention discloses an epoxide hydrolase mutant and a construction method and application of a co-immobilized enzyme of the epoxide hydrolase mutant. The inventor firstly constructs a recombinant expression vector of epoxide hydrolysis MdEH, then constructs a recombinant expression vector of point mutation MdEH-K71I on the basis, then constructs an MdEH-K71I recombinant expression vector suitable for being used in bacillus subtilis, and then replaces a promoter and a signal peptide in the expression vector. The modified recombinant expression vector is used for transforming bacillus subtilis, so that efficient secretory expression of the epoxide hydrolase in a bacillus subtilis expression system is realized. The process conditions of co-immobilization of epoxide hydrolase and halohydrin dehalogenase are further explored, ECR8285 resin is selected as an immobilization carrier, and the conversion rate of glycerin generated by hydrolysis finally reaches 80.29%.

A first aspect of the invention relates to a method of treating or preventing tissue damage, or treating or preventing tissue destruction, in a subject, said method comprising administering to the subject a therapeutically or prophylactically effective amount of a soluble epoxide hydrolase (sEH) inhibitor. A further aspect of the invention relates to a method of treating or preventing leishmaniasis in a subject, said method comprising administering to the subject a therapeutically or prophylactically effective amount of a soluble epoxide hydrolase inhibitor.

A fusion protein and an immobilized enzyme including the fusion protein are provided. The fusion protein includes an epoxide hydrolase active domain and a chitin protein binding domain. Efficient immobilization of epoxide hydrolase is achieved through the specific affinity between chitin and the fusion protein, and ethylhexyl glycidyl ether is used as a substrate to efficiently produce ethylhexylglycerin with the immobilized enzyme. The immobilization method offers advantages such as low cost, high enzyme immobilization efficiency, minimal enzyme activity loss, and strong specificity, fundamentally solving issues like poor recyclability and low stability of free enzymes, as well as low repeatability in traditional whole-cell immobilization methods. It resolves issues such as deep color and protein residues in downstream separation and purification.

The application provides a stilbene compound, a pharmaceutical composition and application thereof, relates to the technical field of medicinal chemistry, and the main skeleton of the compound is a stilbene with a urea group; a series of high-activity stilbene compounds are obtained by expanding different substituents on both sides of the urea group and synthesizing a stilbene side skeleton containing an advantage structure of a natural product; the IC50 value of the high-activity stilbene compound to soluble epoxide hydrolase inhibition reaches the nanomolar level, indicating that the stilbene compound has a high inhibition effect on soluble epoxide hydrolase inhibition enzyme, so that the inhibition effect on inflammation can be realized by inhibiting soluble epoxide hydrolase inhibition enzyme, and the stilbene compound has a good application prospect.

The present invention discloses an epoxide hydrolase mutant and its application in asymmetric synthesis ( S The present invention relates to the application of )-flutriafol epoxy intermediates in the field of enzyme engineering technology. The present invention obtains an epoxide hydrolase mutant with improved enantioselectivity by site-directed mutagenesis of epoxide hydrolase. Rp EH H336W / L360F Compared with the wild type, the epoxide hydrolase mutant Rp EH H336W / L360F right rac The enantioselectivity of the flutriafol epoxy intermediate is significantly improved. Compared with expensive chiral chromatography separation methods, this method provides an environmentally friendly, simple process, and low-cost method for the synthesis of single enantiomers of flutriafol, which has great application prospects.

The invention provides methods for treating, suppressing, or preventing detrimental cytokine and / or lipid mediator surges that can result from a variety of different diseases, conditions, and therapeutic treatments, e.g., by inhibition of cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH).

The present application relates to a kind of sulfonylurea compounds as shown in formula I, preparation method and its application.The compound of the present application has soluble epoxide hydrolase (sEH) inhibitory activity, can increase the level of epoxyeicosatrienoic acid (EETs), and then reduce inflammatory response, can be used for the prevention and treatment of heart failure.The preparation method of the present application has the technical advantages of simple steps, high yield and easily available raw materials.

The invention provides a piperidinyl urea compound as shown in a formula (I), and the compound has efficient soluble epoxide hydrolase inhibitory activity and good in-vivo oral anti-inflammatory activity.

This invention discloses a method for preparing (R)-tebuconazole epoxide intermediates using an epoxide hydrolase mutant, belonging to the field of biocatalysis technology. The preparation of chiral tebuconazole single enantiomers is limited by separation and asymmetric synthesis techniques, making large-scale production impossible. This invention provides a recombinant strain *E. coli* / Rpeh expressing a *Rhodotorula paludinis* epoxide hydrolase mutant. M Using whole cells as catalysts, the 200 mM racemic epoxy intermediate was hydrolyzed and resolved under the conditions of 30 °C and pH 7.5, yielding an ee value of 84% and a yield of 28.9% for the preparation of (R)-tebuconazole epoxy intermediate. This method has advantages such as mild reaction conditions, environmentally friendly catalytic activity, high product optical purity, and high substrate tolerance. It provides other key chiral prerequisites for the preparation of (R)-tebuconazole single enantiomers and has the potential for industrial application.

The invention belongs to the technical field of biological catalysis, and particularly relates to a method for catalyzing hydrolysis of oxetane by using a series of epoxy hydrolase. According to the method, epoxy hydrolase in 23 databases is mined and represented through the technologies of gene mining, heterologous expression and the like, and it is determined that epoxy hydrolase and the like from metagenome DNA (Deoxyribonucleic Acid), Rhodococcus erythropolis, Rhodococcus subtilis, Actinomadura namibiensis and Rhodococcus aureus are adopted as catalytic enzymes, and the catalytic enzymes are used for catalyzing 2-phenyl oxetane to generate (S)-1-phenyl-1, 3-propylene glycol, so that the 2-phenyl oxetane can be used for catalyzing 2-phenyl oxetane to generate (S)-1-phenyl-1, 3-propylene glycol, and the application of the 2-phenyl oxetane to prepare the (S)-1-phenyl-1, 3-propylene glycol and the application of the 2-phenyl oxetane to prepare the (S)-1, 3-propylene glycol.

In aspects, the present invention encompasses crystalline forms of soluble epoxide hydrolase inhibitors having a range of characteristics that facilitate formulation and administration. In one aspect, the disclosure provides a method of treating a soluble epoxide hydrolase (sEH) mediated disorder or disease in a subject by administering to the subject a composition of the invention.

The invention discloses an epoxy hydrolase mutant with high enantioselectivity and application of the epoxy hydrolase mutant in preparation of an (R)-tebuconazole epoxy intermediate, and belongs to the field of biological catalysis. An epoxy hydrolase mutant RtEHY361F with improved enantioselectivity is obtained through site-directed mutagenesis of epoxy hydrolase, 10 mM rac-tebuconazole is subjected to hydrolytic kinetic resolution under the conditions that the temperature is 25 DEG C and the pH value is 7.0, compared with a wild type, the ees of the epoxy hydrolase mutant to a rac-tebuconazole epoxy intermediate is improved from 76.8% to 99.7%, the yield is improved from 33.1% to 34.25%, and the yield is improved from 33.1% to 34.25%. It is indicated that the mutant RtEHY361F has higher selectivity on (R)-tebuconazole in the catalysis process, so that generation of by-products is effectively reduced, the chiral purity is improved, and the mutant RtEHY361F has a high application prospect.

This application discloses an epoxide hydrolase gene cloned from Angelica dahurica. AdEH1 and AdEH2 and its encoded proteins and applications, among which, AdEH 1 and AdEH2 The nucleotide sequences are shown in SEQ ID NO: 1 and SEQ ID NO: 2, respectively, and the amino acid sequences encoding the proteins are shown in SEQ ID NO: 3 and SEQ ID NO: 4, respectively. AdEH1 and AdEH2 The encoded protein possesses epoxide hydrolase catalytic activity, capable of catalyzing the oxidation of imperatorin and angelica root to produce hydrated oxidized imperatorin and angelica root. This application identifies the gene. AdEH1 and AdEH2 Its key role in the biosynthesis of furanocoumarins provides core gene resources for the regulation and green large-scale synthesis of furanocoumarin components in Angelica dahurica, and also provides technical support for the accurate detection of related compounds.