42 results about "Ornithine decarboxylase" patented technology

The present invention provides methods and compositions for modulating polyamine pathway activity as a means for ameliorating neurodegenarative disorders. In particular, for ameliorating the symptoms or onset of amyotrophic lateral sclerosis (ALS) by modulating the gene and protein products involved the polyamine pathway, such as by inhibiting the enzyme, ornithine decarboxylase (ODC), involved in the synthesis of the polyamine, putrescine. Compositions and methods are disclosed for inhibiting the polyamine pathway producing lower polyamine levels resulting in a beneficial effect on ALS. This can be accomplished by using modulating agents such as analogs, or polyamine analogs, and antiproliferative drugs. Screening assays for pharmacological agents that are capable of decreasing polyamine levels and / or reducing cell proliferation are also disclosed.

The present invention relates to nucleotide sequences encoding polypeptides with cis-aconitic decarboxylase activity, the cells transformed with such nucleotide sequences, preferably fungal or plant cells, and to methods wherein such transformed cells are use for the production of itaconic acid.

The present invention relates to a putrescine-producing microorganism and a method for producing putrescine using the same. To be more specific, the present invention is directed to a microorganism given the ability to produce putrescine which is generated by blocking a biosynthetic pathway from ornithine to arginine, increasing the intracellular level of glutamate, enhancing the biosynthetic pathway of ornithine from glutamate, and introducing extracellular ornithine decarboxylase; and a method for producing putrescine by using the microorganism.

The invention belongs to the field of biomedicine and relates to a small molecule inhibitor of ornithine decarboxylase (ODC) and an application thereof. A novel small molecule inhibitor aiming at ODC is found through computer-aided high-throughput medicine screening. Verification of the effects of the novel small molecule inhibitor finds that the novel small molecule inhibitor has good inhibiting effects on ODC and can be especially used for inhibiting human-derived ODC, preventing, treating and diagnosing tumor diseases and pathogenic microorganism infection and developing and preparing tumor medicines or medicines against pathogenic microorganism infection.

The invention relates to a high-level soluble expression method and application of recombined tyrosine decarboxylase, belongs to the technical field of enzyme engineering, and relates genetically engineered strain E. coliBL21(DE3) / pET24-TDC for recombined expressed lactobacillus brevis tyrosine decarboxylase, a construction method of the genetically engineered strain, a high-level soluble expression method for the TDC and application of the TDC. A TDC encoding gene is connected to an expression vector and passed to an escherichia coli expression host; glucose is added to fermentation medium; accordingly, soluble expression of the recombined TDC (rTDC) can be increased significantly, protein yield is up to 224mg / L from fermentation broth. The rTDC with His-Tag at the Ni column purified C-end is used, so that the recovery rate is 90%. The rTDC has 133.5U / mg specific enzyme activity against substrate L-tyrosine. The soluble expression method of the rTDC has the advantages of high expression level, purification simplicity, high recovery rate, low cost and the like and can be applied to the preparation of tyramine and dopamine and the treatment study on Parkinson's disease.

Green fluorescent protein (GFP) is widely used as a reporter in determining gene expression and protein localization. The present invention provides fusion proteins with a half life of ten hours or less with several embodiments having half lives of 4 hours or less. Such proteins may be constructed by fusing C-terminal amino acids of the degradation domain of mouse ornithine decarboxylase (MODC), which contains a PEST sequence, to the C-terminal end of an enhanced variant of GFP (EGFP). Fluorescence intensity of the fusion protein in transfected cells is similar to that of EGFP, but the fusion protein, unlike EGFP, is unstable in the presence of cycloheximide. Specific mutations in the MODC region have resulted in mutants with varying half lives, useful for a variety of purposes.

The invention discloses a glycosyl-transferbeta-galactosidase production bacterium, which is characterized by the following: the name of this bacterium is Enterobacter cloacae B5, which is Gram-negative bacterium; the conservation code is CGMCC No.1401; the bacterium shape changes along culture time extension on the LB culture medium from long rod to short rod, ellipsoid shape and ball; the colouring size is 0.5-1.5*0.7-9.0 mm with single, couple or short-chain arrangement; the bacterium can move by peripheral flagellar without gemma and can apply citrate or acetate as only one carbon source, which products acid and gas by fermenting glucose at 37 deg.c and glycerin without gas, hydrolyzing aesculin and indole; V.P. detects positive and methyl red detects negative; the nitrate is reduced and Lys is not decarboxylation with ornithine decarboxylase, arginine dihydrolase and urease; the nucleotide sequence of this bacterium 16S rDNA is described as SEQ ID No.1; the beta-galactosidase can take lactin as substrate, which catalyzes to produce oligomer galactose.

The invention relates to a genetically-engineered strain streptomyces diastatochromogenes with high production of epsilon-polylysine. The streptomyces diastatochromogenes is obtained by over-expressing three key genes, in different metabolic pathways, of a succinate dehydrogenase gene sdhB, a lysine / ornithine decarboxylase gene dcdA and an asparagine synthetase gene asnO in streptomyces diastatochromogenes TUST separately. According to the genetically-engineered strain streptomyces diastatochromogenes with high production of the epsilon-polylysine, by over-expressing the key genes in the different metabolic pathways, the genetically-engineered recombinant strain is obtained, and an experiment proves that the epsilon-polylysine-producing capability of the streptomyces genetically-engineeredstrain is improved compared with that of the original strain streptomyces diastatochromogenes TUST in the same situation, so that the excellent strain is provided for production of epsilon-polylysine.

The present invention relates to a putrescine-producing microorganism and a method for producing putrescine using the same. To be more specific, the present invention is directed to a microorganism given the ability to produce putrescine which is generated by blocking a biosynthetic pathway from ornithine to arginine, increasing the intracellular level of glutamate, enhancing the biosynthetic pathway of ornithine from glutamate, and introducing extracellular ornithine decarboxylase; and a method for producing putrescine by using the microorganism.

The invention relates to chlorine proof microorganism. It is chlorine proof strain No.1. Its features are as follows: it is brevibacterium linens B723-1 CCTCC NO.M205122; its colonial morphologies are creamy white, rule circular, un-transparent, smooth, stiff, and pink after 5M KOH processing; physiological characteristics that young bacterial is irregular baculiform, 0.6-1.2um*1.5-6.0um, single or pairs arrangement, common V shape; old is irregular globular, and gram positive; its main biological and chemical features are concurrently character anaerobic, chemoheterotrophic bacteria, contacting enzyme positive, oxidase negative, producing arginine double hydrolase, lysine decarboxylase, ornithine decarboxylase, and urease, and producing acid from glucose, no moving, no spore; its optimum temperature is 25-37 centigrade degree. It can live in high concentration chloride ion condition, and high effectively degrade high concentration organic pollutant.

(±)-alpha-(Difluoromethyl)-ornithine is separate into its isomers using (-)-O,O'-di-p-toluoyl-L-tartaric acid. (-)-alpha-(Difluoromethyl)-ornithine monohydrochloride monohydrate and in particular the (-)-isomer are inhibitors of ornithine decarboxylase and thereby have numerous pharmacological actions.

One example embodiment is a method of treating lung carcinoma in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of an arginine reducing compound and a therapeutically effective amount of an ornithine decarboxylase (ODC) inhibitor to provide a combination therapy that has a synergistic therapeutic effect compared to an effect of the arginine reducing compound and an effect of the ODC inhibitor, in which each of the arginine reducing compound and the ODC inhibitor is administered alone.

In accordance with the present invention, there are provided novel Siah-Mediated-Degradation-Proteins (SMDPs) and / or SCF-Complex Proteins (SCPs). Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention SMDPs and / or SCPs can be employed in a variety of ways, for example, for the production of anti-SMDP and / or SCP antibodies thereto, in therapeutic compositions, and methods employing such proteins and / or antibodies for drug screening, functional genomics and other applications. Also provided are transgenic non-human mammals that express the invention protein. Also provided are compositions and methods for targeting the destruction of selected polypeptides in eukaryotic cells based on the ubiquitin-independent mechanism by which ornithine decarboxylase is degraded by the 26S proteasome.

The invention belongs to the technical field of chiral compounds biological transformation separation, in particular relates to a method for preparing chiral organic coumounds and a method for preparing D-ornithine and putrescine, and is also suitable for preparing other D-ornithine compounds and aliphatic amine. The method for preparation comprises: mixing L-arginine or salt of the L-arginine with salicylal or derivant of the salicylal according to proportion, dissolving in alkaline or acidic dissolvant, obtaining DL-ornithine after racemization reaction, taking the DL-ornithine, biotransforming with microorganism or enzyme which contains lysine decarboxylase or ornithine decarboxylase under the temperature from 25DEG C to 45DEG C, obtaining the D-ornithine and the putrescine, then, using an isoelectric point crystallization method or a cation exchange resin separation method to separate the D-ornithine and the putrescine, and obtaining optically pure D-ornithine and putrescine. A chemical racemization method of the invention main takes water as the dissolvant, the catalyst consumption is little, the dissolvant which is used does not have poison and has low cost, the microorganism is easily cultured, and the invention is suitable for large scale industrial production.

The invention belongs to the field of biomedicine and relates to a small molecule inhibitor of ornithine decarboxylase (ODC) and an application thereof. A novel small molecule inhibitor aiming at ODC is found through computer-aided high-throughput medicine screening. Verification of the effects of the novel small molecule inhibitor finds that the novel small molecule inhibitor has good inhibiting effects on ODC and can be especially used for inhibiting human-derived ODC, preventing, treating and diagnosing tumor diseases and pathogenic microorganism infection and developing and preparing tumor medicines or medicines against pathogenic microorganism infection.

The invention relates to an anisodus luridus ornithine decarboxylase ALODC gene as well as a recombinant expression vector and application thereof. By cloning the anisodus luridus ornithine decarboxylase ALODC gene, through an agrobacterium tumefaciens mediation method, the gene is transferred into anisodus luridus, a transgenic plant is obtained, after ALODC over-expression is conducted, the contents of putrescine and tropane alkaloids in the anisodus luridus plant can be significantly improved, and an ideal method is provided for effectively producing hyoscyamine and scopolamine by means ofa transgenic technology.

The invention provides a small-molecule inhibitor containing dihydracridine. The small-molecule inhibitor is 2, 2-dimethyl-N-(6-methyl-4-oxo-3, 4-dihydro-2-acridinyl) propanamide. The structural formula of the inhibitor is shown in the description. The small-molecule inhibitor containing the dihydracridine is applied to inhibiting the ornithine decarboxylase (ODC) and preparing medicine used for treating tumors and medicine used for treating pathogenic microorganism infection, and significant effects are achieved.

The invention discloses a mesothelin-ODC422-461 fusion protein expressed by DCs (dendritic cells) and application of the mesothelin-ODC422-461 fusion protein. The fusion protein is a protein consisting of an amino acid sequence as shown in SEQ ID NO. 1, and is formed by fusing the mesothelin protein and amino acid at site C-422-461 of mouse ornithine decarboxylase, and the DCs are derived from DCs differentiated from monocyte in PBMCs, DCs differentiated from iPS / ES induction, and primary DC cells separated from blood. The fusion protein can be used for inducible expression in DC cells, tumor antigen presentation of the DCs is facilitated, the antigen presentation efficiency of in-vivo T cells is improved, the T cells are activated to kill tumor cells, and in addition, the fusion protein can be used for cell therapy since the half-life period of the fusion protein is very short, the fusion protein serving as medicine has small toxicity and small side effects, and can generate synergistic effects with immune cells.

The invention belongs to the technical field of chiral compounds biological transformation separation, in particular relates to a method for preparing chiral organic coumounds and a method for preparing D-ornithine and putrescine, and is also suitable for preparing other D-ornithine compounds and aliphatic amine. The method for preparation comprises: mixing L-arginine or salt of the L-arginine with salicylal or derivant of the salicylal according to proportion, dissolving in alkaline or acidic dissolvant, obtaining DL-ornithine after racemization reaction, taking the DL-ornithine, biotransforming with microorganism or enzyme which contains lysine decarboxylase or ornithine decarboxylase under the temperature from 25DEG C to 45DEG C, obtaining the D-ornithine and the putrescine, then, using an isoelectric point crystallization method or a cation exchange resin separation method to separate the D-ornithine and the putrescine, and obtaining optically pure D-ornithine and putrescine. A chemical racemization method of the invention main takes water as the dissolvant, the catalyst consumption is little, the dissolvant which is used does not have poison and has low cost, the microorganism is easily cultured, and the invention is suitable for large scale industrial production.

The invention provides a small-molecule inhibitor containing benzo dioxole. The small-molecule inhibitor is N'-({6-nitro-1,3-benzo dioxole-5-radical} methylene) spiro [2.3] hexane-1-carbohydrazide, and the structural formula of the inhibitor is shown in the description. The small-molecule inhibitor containing the benzo dioxole is applied to inhibiting the ornithine decarboxylase (ODC) and preparing medicine used for treating tumors and medicine used for treating pathogenic microorganism infection, and significant effects are achieved.

The invention provides a small molecule inhibitor containing 2,6-dihydroxypurine, the small molecule inhibitor is 1,3-dimethyl-8-(2-thienyl)-3,7-dihydro-1H- Purine-2,6-diketone, its structural formula is: the present invention will contain the 2,6-dihydroxypurine small molecule inhibitor in the application of inhibiting ornithine decarboxylase (ODC), and in the preparation of the drug for treating tumor application, and in the preparation of medicines for the treatment of pathogenic microorganism infections, and achieved remarkable results.

The invention provides an engineering bacterium capable of expressing ornithine decarboxylase, a treatment method of an ornithine-containing solution and a kit. The engineering bacterium comprises a nucleotide sequence for encoding ornithine decarboxylase. The treatment method of the ornithine-containing solution comprises the following steps: obtaining the ornithine-containing solution which comprises D-ornithine and L-ornithine; culturing engineering bacteria capable of expressing ornithine decarboxylase to obtain an ornithine decarboxylase crude enzyme solution; and conducting enzyme treatment: adding the ornithine decarboxylase crude enzyme solution and pyridoxal phosphate into the ornithine-containing solution, and reacting to generate a final product which contains D-ornithine and / orbutanediamine. The kit contains the ornithine decarboxylase crude enzyme solution. According to the treatment method of the ornithine-containing solution, DL-ornithine is converted into butanediamineand D-ornithine, the butanediamine and the D-ornithine are easy to separate, the product purity and the optical purity are improved, the product yield is increased, and the separation cost is reduced.

The present invention discloses method of detecting primary hypertension susceptibility. The detection includes detecting individual ornithine decarboxylase 1 gene ODC1, transcript and / or protein, comparing with normal items to find the existing variation, which shows the greater attack probability of the individual in primary hypertension. The present invention also discloses the corresponding detection kit.

The invention provides a small molecule inhibitor containing dihydroacridine, the small molecule inhibitor is 2,2-dimethyl-N-(6-methyl-4-oxo-3,4-dihydro-2 ‑acridinyl) propionamide, the structural formula is the application of the small molecule inhibitor containing dihydroacridine in inhibiting ornithine decarboxylase (ODC) of the present invention, and the application in the preparation of drugs for treating tumors, and in The application in the preparation of medicines for the treatment of pathogenic microorganism infections has achieved remarkable results.

Green fluorescent protein (GFP) is widely used as a reporter in determining gene expression and protein localization. The present invention provides fusion proteins with a half life of ten hours or less with several embodiments having half lives of 4 hours or less. Such proteins may be constructed by fusing C-terminal amino acids of the degradation domain of mouse ornithine decarboxylase (MODC), which contains a PEST sequence, to the C-terminal end of an enhanced variant of GFP (EGFP). Fluorescence intensity of the fusion protein in transfected cells is similar to that of EGFP, but the fusion protein, unlike EGFP, is unstable in the presence of cycloheximide. Specific mutations in the MODC region have resulted in mutants with varying half lives, useful for a variety of purposes.

The present invention provides a kind of benzamide small molecule inhibitor, and this small molecule inhibitor is 2,3,4,5,6-pentafluoro-N-(3-fluoroalkenyl) benzamide, and structural formula is as follows: The present invention The application of the benzamide small-molecule inhibitor in inhibiting ornithine decarboxylase (ODC), in the preparation of a drug for treating tumors, and in the preparation of a drug for treating pathogenic microorganism infection has achieved remarkable effects.

The invention provides methods, uses and compounds for treating cancers. For example, certain embodiments provide a method for treating cancer in a mammal comprising administering to the mammal an effective amount of 3,5,7,8,4′-Pentahydroxyflavone, or a pharmaceutically acceptable salt thereof. Certain other embodiments of the invention provide methods for inactivating ornithine decarboxylase (ODC) in a cell comprising contacting the cell in vitro or in vivo with an effective amount of 3,5,7,8,4′-Pentahydroxyflavone, or a pharmaceutically acceptable salt thereof. The invention also provides a dermal product comprising 3,5,7,8,4′-Pentahydroxyflavone, or a pharmaceutically acceptable salt thereof, wherein the product prophylactically or therapeutically treats sunburn or other sun exposure and / or skin cancer in a mammal.