147 results about "Epoxide metabolism" patented technology

The invention discloses methods of using cis-epoxyeicosantrienoic acids (“EETs”), inhibitors of soluble epoxide hydrolase (“sEH”), or a combination of an EET and an inhibitor of sEH, to reduce or prevent niacin-induced cutaneous vasodilation (“flushing”) in subjects suffering from this undesirable side effect of receiving therapeutic amounts of niacin.

Disclosed are sulfonamide compounds of formula (I), wherein R-R, Y and m are as defined in the claims, and compositions that inhibit soluble epoxide hydrolase (sEH), methods for preparing the compounds and compositions, and methods for treating patients with such compounds and compositions. The compounds, compositions, and methods are useful for treating a variety of sEH-mediated diseases, including hypertensive, cardiovascular, inflammatory, pulmonary, and diabetes-related diseases.

The invention provides compounds that inhibit epoxide hydrolase in therapeutic applications for treating hypertension. A preferred class of compounds for practicing the invention have the structure shown by Formula 1 wherein Z is oxygen or sulfur, W is carbon phosphorous or sulfur, X and Y is each independently nitrogen, oxygen, or sulfur, and X can further be carbon, at least one of R1-R4 is hydrogen, R2 is hydrogen when X is nitrogen but is not present when X is sulfur or oxygen, R4 is hydrogen when Y is nitrogen but is not present when Y is sulfur or oxygen, R1 and R3 is each independently C1-C20 substituted or unsubstituted alkyl, cycloalkyl, aryl, acyl, or heterocyclic.

It has now been discovered that inhibitors of soluble epoxide hydrolase (“sEH”) are useful in reducing the severity of or inhibiting the progression of obstructive pulmonary diseases, restrictive airway diseases, and asthma. Administering a cis-epoxyeicosantrienoic acid (“EET”) in addition to the inhibitor is at least additive, and may be synergistic, in reducing or inhibiting these conditions and diseases, as measured by reduced numbers of neutrophils present in the lung. The inhibitor of sEH may be a nucleic acid, such as a small interfering RNA.

The invention discloses a kidney bean epoxide hydrolase mutant with improved catalytic activity and enantioconvergent property, belonging to the fields of genetic engineering and protein expression. A strain of epoxide hydrolase mutant PvEH1 <L105I/ M160A/ M175I> with improved catalytic activity and enantio-convergent property can be obtained by reforming the molecular structure of epoxide hydrolase (EH) by means of a site-directed mutation biotechnology on the basis of EH with certain enantio-convergent catalysis characteristic. The mutant has the advantages of high enantio-selectivity and high catalytic activity, thus having greater application potential and also laying a theoretical foundation for the study of the EH.

The invention belongs to the field biotechnology and discloses use of an RT-PCR method in cloning an epoxide hydrolase gene (PchEHA) from a BKM-F1767 strain (Phanerochaete chrysosporium BKM-F1767) of fungus Phanerochaete chrysosporium and a nucleotide sequence and an amino acid sequence of a coding region of the PchEHA. Cloned plasmid pTEHA containing the gene, a recombinant expression plasmid pET28EHA containing the gene and a genetic engineering strain Escherichia coli E.coli BL21(DE3)/PeT28EHA containing the PchEHA gene are provided to prepared the recombinant epoxide hydrolase. The epoxide hydrolase of the invention has catalytic activity for various epoxides and shows enantiomer selectivity of different degrees, particularly high enantiomer selectivity for epoxyethylbenzene. The recombinant epoxide hydrolase of the invention can be used in the fields of the kinetic resolution of a chiral epoxide racemic mixture, the asymmetric catalysis of epoxides, and the like.

The invention discloses an epoxide hydrolase sourced from Phaseolus vulgaris and an application thereof and belongs to the technical field of biology. The invention discloses an epoxide hydrolase gene (pveh2) sourced from a leguminous plant, Phaseolus vulgaris, as well as a corresponding amino sequence. The invention provides a recombinant plasmid pET28a(+)-pveh2 and a genetic engineering bacteria E.coli BL21(DE3)/pET28a(+)-pveh2, which comprise the gene. A recombinant epoxide hydrolase is prepared through expression by the bacterial strain. The invention provides a method of biocatalysis through fermentation with an enzyme produced by the recombinant bacterial strain constructed in the invention, thus producing enantiomerically pure R-type styrene oxide (ee > 99%); in addition, final yield can reach 49.3%, which is approximate to a theoretical value, 50%.

The invention discloses an epoxide hydrolase mutant as well as a gene and an application of the epoxide hydrolase mutant. The epoxide hydrolase mutant is protein which is obtained by substituting one amino acid at one site or multiple sites of the 123th, 128th, 144th 145th, 168th, 219th and 221st amino acid of the protein with an amino acid sequence as shown in SEQ ID No: 1 in a sequence table and deriving from the protein with the amino acid sequence as shown in SEQ ID No: 1 and has epoxide hydrolase activity. Compared with wild type epoxide hydrolase, the epoxide hydrolase mutant provided by the invention can greatly improve hydrolytic activity and enantioselectivity of the racemization epoxide, and is particularly suitable for splitting and catalyzing the racemization naphthyl glycidyl ether to prepare (S)- naphthyl glycidyl ether and further synthesize racemic medicament (S)-propranolol. The hydrolase mutant has good industrial application prospect.

The invention belongs to the technical field of biology, and provides a method for preparing chiral beta-amino alcohol by asymmetric amine hydroxylation of an olefin compound through cascade biocatalysis. Olefin monooxygenase, epoxide hydrolase, alcohol dehydrogenase and transaminase are taken as biocatalysts; olefin is used as a substrate and a reaction is performed in a phosphate buffer solutionto synthesize the chiral beta-amino alcohol. The conversion rate reaches up to 99% and the ee value is 97-99%. The olefin monooxygenase/alcohol dehydrogenase (ADH)/(R)-(+)-1 phenylethylamine (R-MBA)in a cascade biocatalytic system drives the reaction to be carried out towards a direction beneficial for product generation, and a cofactor NAD<+> is regenerated. The whole-cell cascade biocatalysisis realized through using engineering recombinant escherichia coli cells, and the chiral beta-amino alcohol is obtained. The method is used for converting the cheap olefin compound into various different chiral beta-amino alcohols; the catalytic efficiency is high, reaction conditions are mild, a reaction process is simple, the energy consumption is low, and the method is in line with the principle of green chemistry.

The invention discloses an epoxide hydrolase mutant, an engineering bacteria and application of the epoxide hydrolase mutant. The epoxide hydrolase mutant is obtained by carrying out single-point mutation or multi-point mutation on amino acid in the 182rd position, the 207th position and/or the 240th position of an amino acid sequence represented by SEQ ID NO.13. Compared with the wild type epoxide hydrolase, the epoxide hydrolase mutant provided by the invention has higher catalytic activity and stereoselectivity; and the epoxide hydrolase mutant is particularly applied to preparing (S)-epoxy chloropropane by splitting racemic epichlorohydrin.

The invention discloses an epoxide hydrolase mutant and its application. The mutant is the 108th isoleucine or the 131st aspartic acid or the 247th aspartic acid in the amino acid sequence shown in SEQ ID NO.2. Threonine is obtained by carrying out single mutation, double mutation or triple mutation; compared with the unmutated epoxide hydrolase mutant, the enzymatic activity, stereoselectivity and stability of the epoxide hydrolase mutant according to the present invention Significantly improved; Among them, the specific enzyme activity of the mutant was improved by 5.4 times compared with the original enzyme, reaching 315.2U/mg, the half-life was improved by 12.8 times, the enantioselective E value was improved by 2.1 times, and the epoxide hydrolase mutant was In the two-phase system, 800mM racemic epichlorohydrin can be catalytically resolved, and the yield of R-epichlorohydrin reaches more than 90% of the theoretical yield, and the enantioselectivity is greater than 99%.

The present invention is related to an isolated and purified nucleotide sequence from microbial origin, encoding an epoxide hydrolase, the vector comprising said nucleotide sequence, the recombinant host cell transformed by said nucleotide sequence and the epoxide hydrolase amino acid sequence encoded by said nucleotide sequence and/or expressed by said recombinant host cell.

The invention discloses an epoxide hydrolase and a preparation method thereof. The amino acid of the 163rd site of the main body amino acid sequence of the epoxide hydrolase is phenylalanine, the main body amino acid sequence of the epoxide hydrolase is SEQ ID No: 10, and the epoxide hydrolase is coded by DNA molecules (expressed as SEQ ID No: 9) of the main body amino acid sequence. The preparation method for the epoxide hydrolase comprises that: tyrosine of the 163rd site of the main body amino acid sequence of the wild epoxide hydrolase is substituted by using the phenylalanine, the main body amino acid sequence of the wild epoxide hydrolase is SEQ ID No: 4, and the wild epoxide hydrolase is coded by DNA molecules (expressed as SEQ ID No: 3) of the main body amino acid sequence. Compared with the wild epoxide hydrolase, the epoxide hydrolase has high temperature stability and maintains high enzyme activity, can be used for hydrolyzing cis-epoxysuccinic acid or L (+)-tartaric acid or salt thereof, and prolongs the service life of a biocatalyst in the industrialized production.

Provided are methods for treating, reducing, alleviating, and/or inhibiting neuropathic pain by orally, intravenously or intrathecally administering an effective amount of an inhibitor of soluble epoxide hydrolase (“sEH”), to a patient in need thereof. The neuropathic pain treated is selected from the group consisting of post-herpetic neuralgia, trigeminal neuralgia, focal peripheral nerve injury, and anesthesia dolorosa, central pain due to stroke or mass lesion, spinal cord injury, or multiple sclerosis, and peripheral neuropathy due to diabetes, HIV, or chemotherapy.