82 results about "Cyclase" patented technology

The invention provides a compound serving as a glutamine cyclase inhibitor and application of the compound, and belongs to the field of medical chemistry. The structure of the compound is shown as a formula I. The compounds have good inhibitory activity on sQC and gQC enzymes and mutants thereof, and the half inhibitory concentration of most compounds reaches the sodium mole level, so that the compounds can be used for preparing glutamine cyclase inhibitors. In addition, the compounds can also be used for preparing medicines for preventing and treating diseases related to glutamine cyclase. The invention lays a material basis for research and development of glutamine cyclase inhibitor drugs, and has a good application prospect. Formula I.

This invention relates to the application of exosomes in reversing tumor resistance to immune checkpoint (PD-1) inhibitors. A novel application of exosomes in the preparation of pharmaceutical compositions reversing tumor resistance to immune checkpoint inhibitors is disclosed. Exosomes generated from tumor cells recombinantly expressing adenylate cyclase 7 (ADCY7) can significantly reverse tumor resistance to PD-1 inhibitors, and the exosomes exhibit a synergistic effect with the PD-1 inhibitors.

The invention relates to a crystal form of a compound shown as a formula I or a pharmaceutically acceptable salt thereof and a preparation method of the crystal form of the compound shown as the formula I or the pharmaceutically acceptable salt thereof. The compound of the formula I or the pharmaceutically acceptable salt thereof is used for treating cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, heart failure, pulmonary arterial hypertension (WHO levels I, II, III, IV), angina pectoris, thrombus, restenosis, myocardial infarction, stroke, cardiac insufficiency, fibrosis, pulmonary hyperplasia, erectile dysfunction, asthma, chronic kidney disease, diabetes, and the like. The composition can be used for treating liver cirrhosis, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome, acute lung injury, pulmonary fibrosis, cystic fibrosis or interstitial lung disease.

The invention belongs to the technical field of biological medicines, and particularly relates to a multifunctional peptide and application thereof in anti-inflammatory, antibacterial, mucous membrane repair and intestinal secretion promotion. Specifically, the invention designs a polypeptide and an analogue which have guanylate cyclase C receptor (GUCY2C) agonist activity and anti-inflammatory, antibacterial and mucous membrane repair functions at the same time. The polypeptide can be combined with GUCY2C, stimulate generation of cyclic guanosine monophosphate (cGMP) in cells, promote intestinal fluid secretion, inhibit release of proinflammatory factors, relieve inflammatory response, promote repair of intestinal injury mucosa, inhibit growth of opportunistic pathogenic bacteria and accelerate intestinal homeostasis recovery after intestinal preparation. The composition can effectively promote intestinal tract cleaning, does not cause intestinal inflammation and mucosal lesion, has no hemolytic toxicity and cytotoxicity, is high in safety, and has a good clinical application prospect.

This invention discloses a genetically engineered bacterium capable of synthesizing large quantities of natural cyclic diguanylate (c-di-GMP) and its applications. It involves knocking out the major phosphodiesterase gene chr1_233 as described in claim 1 within the sphingobium xenophagum C2 strain. This invention rationally designs and modifies the c-di-GMP synthesis and degradation pathways and the inhibitory site of major diguanylate cyclase activity in heterologous sphingobium-consuming bacteria, constructing a series of genetically engineered bacteria capable of synthesizing large quantities of natural c-di-GMP. This provides the industry with a green, simple, economical, and efficient method for producing natural c-di-GMP, and offers a series of high-quality and inexpensive raw materials for the preparation of STING agonists or immune adjuvants, or for the preparation of drugs for treating diseases related to STING protein function.

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 present disclosure provides combinations of GLP-1 receptor agonists, and guanylate-cyclase C (GC-C) receptor agonists, and pharmaceutical compositions comprising the same. Also described are methods of making and using the combination, which can be used to treat or prevent of one or more side effects of a GLP-1 receptor agonist.

This invention discloses a guanylate cyclase-C (GC-C) activating peptide and its applications, belonging to the field of bioactive peptide technology. The amino acid sequence of the GC-C activating peptide is PFPGPIPN. The GC-C activating peptide of this invention can significantly activate GC-C activity, increasing intracellular cGMP levels. Furthermore, the GC-C activating peptide of this invention can alleviate constipation and abdominal pain symptoms in mice, thereby effectively preventing or improving irritable bowel syndrome (IBS). Therefore, the GC-C activating peptide provided by this invention has advantages such as high activity, safety and non-toxicity, and good water solubility. It can be used as a candidate molecule for alternative or adjuvant drugs in the clinical treatment of IBS, and also as a health product or food to improve constipation or abdominal pain.

A pharmaceutical composition includes a combination of a guanylate cyclase C (GUCY2C) agonist and a short-chain C2 to C5 fatty acid and / or a salt and / or a prodrug thereof in a therapeutically effective amount and one or more pharmaceutically acceptable excipients as well as to a method of preventing and / or treating colorectal tumorigenesis and / or carcinogenesis and / or chronic intestinal inflammation and / or cystic fibrosis related gastrointestinal manifestations by administering to a patient, who has developed or is at risk to develop colorectal tumorigenesis and / or carcinogenesis and / or chronic intestinal inflammation and / or cystic fibrosis related gastrointestinal manifestations, a therapeutically effective amount of a combination of a GUCY2C agonist and a short-chain C2 to C5 fatty acid or a salt or a prodrug thereof.

The invention provides recombinant saccharomyces cerevisiae for producing beta-carotene and application of the recombinant saccharomyces cerevisiae, and belongs to the field of genetic engineering. According to the invention, a beta-carotene metabolic pathway is constructed in saccharomyces cerevisiae, screening is carried out on a key gene lycopene cyclase gene in the metabolic pathway, and site-directed mutagenesis is carried out on lycopene cyclase derived from Rhizomucor circinelloides f. Lusitanius, so that a mutant is constructed. According to the invention, the constructed mutant is expressed in saccharomyces cerevisiae, so that the titer of beta-carotene is remarkably improved.

The present disclosure describes compositions and methods of treating solid tumors using chimeric antigen receptor (CAR) T cell (CAR-T) therapy and / or antibodies targeting uanylate Cyclase 2C (GCC. GUCY2C). The compositions include CAR comprising an extracellular domain that binds GCC. Further disclosed are methods of using modified T ceils expressing a CAR that binds GCC for treating different types of carters.

The purpose of the present invention is to provide a method for producing ambrein by which ambrein can be easily and efficiently obtained.　This problem can be solved by a mutant tetraprenyl-β-curcumene cyclase in which aspartic acid that is the fourth amino acid residue of a DXDD motif is substituted by an amino acid other than aspartic acid and the seventh amino acid of a (D / N)G(T / L)(L / F / Y)(Y / F)SY motif is substituted by an amino acid other than tyrosine, said mutant tetraprenyl-β-curcumene cyclase: (a) having nine specific motifs; (b) having 40% or higher sequence identity with the amino acid sequence represented by SEQ ID NO: 1; and (c) showing an ambrein synthesis activity using 8α-hydroxypolypoda-13,17,21-triene as a substrate.

This invention relates to the field of congenital heart disease treatment technology, and discloses the application of sapropterin in the prevention and treatment of bisphenol fluorene-induced congenital heart disease in fetuses. The congenital heart disease includes cardiac structural defects, heart failure, or cardiomyocyte lesions, specifically selected from ventricular septal defects, atrial septal defects, tetralogy of Fallot, myocardial hypertrophy, decreased cardiac ejection fraction, decreased short-axis contraction rate, cardiomyocyte ferroptosis, myocardial tissue inflammatory infiltration, or myocardial collagen fibrosis. Sapropterin is used as a direct supplement to biological tetrahydropterin (BH4). Through exogenous intervention, it precisely reverses the endogenous BH4 deficiency caused by bisphenol fluorene exposure, restores the expression of GTP cyclase 1 (GCH1) and the dynamic balance of RNA m6A, and upregulates the level of YTH domain family protein 2 (YTHDF2), thereby blocking ferroptosis signal transduction, reducing oxidative stress and inflammatory response, and inhibiting the process of myocardial tissue fibrosis at the molecular level.

A method of reducing fear memory in a mammal comprising the step of inhibiting or reducing cAMP signaling in the mammal. The cAMP signaling can be reduced using an adenylyl cyclase 1 (AC1) inhibitor or using a phosphodiesterase, such as a cAMP-specific phosphodiesterase, such as PDE4.

The invention provides a benzylimidazole glutamine cyclase inhibitor as well as a preparation method and application thereof, and belongs to the field of medical chemistry. The compound as shown in the formula I is prepared, the compound has good inhibitory activity on glutamine cyclase, and the half inhibitory concentration of most compounds reaches the nanomole level; the compound has a wide application prospect in preparation of drugs for treating Alzheimer's disease, depression, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, tumor, synovial membrane disease, gout, acute / chronic enteritis, rheumatoid arthritis or inflammatory diseases, and lays a material basis for research and development of related drugs.

The invention discloses a Yarrowia lipolytica engineering bacterium for producing astaxanthin based on a fusion protein method and application of the Yarrowia lipolytica engineering bacterium. A complete astaxanthin synthesis path is expressed in host bacteria by recombinant Yarrowia lipolytica; comprising geranyl geranyl diphosphate synthase CrtE, phytoene synthetase / lycopene cyclase CrtYB, phytoene desaturase CrtI, 3-hydroxy-3-methylglutaryl CoA reductase tHMGR, beta-carotene ketoalcohol enzyme CrtW and beta-carotene hydroxylase CrtZ, and astaxanthin synthesis key enzymes CrtW and CrtZ are subjected to fusion expression by using a short peptide or Linker, so that the astaxanthin is obtained. Meanwhile, the expression of hemoglobin VHb from vitreoscilla is increased; the astaxanthin production performance of the recombinant strain is verified on the basis of protein engineering and fermentation engineering, and the astaxanthin production capacity of the yarrowia lipolytica is further improved.

Compounds of Formula (A-I) or stereoisomers or pharmaceutically acceptable salts thereof as glutamine cyclase inhibitors, processes for their preparation, pharmaceutical compositions containing the compounds of Formula (A-I) or stereoisomers or pharmaceutically acceptable salts thereof, and the Formula (A-I) The invention relates to a use of a compound or a stereoisomer thereof or a pharmaceutically acceptable salt thereof in the prevention or treatment of QPCT and / or QPCTL mediated diseases or conditions including neurodegenerative diseases.

The compositions and methods of the disclosure can be used to produce a cannabinoid in a host cell, such as a yeast cell. For example, the disclosure features host cells (e.g., yeast cells) modified to express one or more enzymes of a cannabinoid biosynthetic pathway, such as an acyl activating enzyme (AAE), a tetraketide synthase (TKS), a cannabigerolic acid synthase (CBGaS), and / or an olivetolic acid cyclase (OAC).

Methods and compositions relate to managing chimeric antigen receptor T (CAR T) cell therapy-associated diarrhea in human subjects undergoing such therapy for colorectal cancer (CRC) are disclosed. The CAR T cells target a CRC-associated antigen, such as Guanylate Cyclase C (GCC) or Carcinoembryonic Antigen (CEA). The methods comprise administering a prophylactic regimen to the subject post-infusion of CAR T cells. This regimen includes agents such as vedolizumab, infliximab, or prophylactic budesonide. Subjects are monitored for diarrhea development and severity based on predefined clinical criteria, including stool frequency or stool volume. The methods may further involve a tiered therapeutic algorithm for treating occurring diarrhea, potentially utilizing corticosteroids or antithymocyte globulin (ATG). These approaches aim to reduce the incidence, duration, and severity of CAR T induced diarrhea, thereby improving patient safety and treatment tolerability.

The present disclosure relates to the use of stimulators of soluble guanylate cyclase (sGC), pharmaceutically acceptable salts thereof and pharmaceutical formulations or dosage forms comprising them, alone or in combination with one or more additional agents, for the treatment of various CNS diseases, wherein an increase in sGC stimulation, or an increase in the concentration of nitric oxide (NO), or cyclic guanosine 3′5′-monophosphate (cGMP) or both, or an upregulation of the NO pathway is desirable.

The invention relates to recombinant escherichia coli for producing nisin and application thereof, and belongs to the technical field of fermentation. Escherichia coli is modified, nisin precursor peptide, SUMO, dehydratase NisB, cyclase NisC and transporter NisT are heterologously expressed, T7, trc and tac promoters are used for regulating and controlling the expression intensity, the titer of the finally obtained nisin is 13521 IU / mL, a new method is provided for heterologously producing the nisin, and the method has a good development prospect and is worthy of popularization and application. The industrial production is facilitated.

Disclosed herein are antibodies, or antigen-binding fragments thereof, that bind to guanylate cyclase C (GUCY2C), multispecific antibodies comprising the same, and methods of treating cancer using the same.

The present invention relates to methods for treating patients with systemic sclerosis, comprising administering to a patient in need thereof a therapeutically effective amount of a soluble guanylate cyclase (sGC) activator of formula (I),or a pharmaceutically acceptable salt thereof, where R1-R7 and A are as defined herein.

The application discloses recombinant escherichia coli for producing isopulegol and a construction method, and the construction method is as follows: a plasmid 1 is obtained by replacing an expression module of pETDuet-1 with an EM nucleotide fragment; a plasmid 2 is obtained by replacing an expression module of pRSFDuet-1 with the EM nucleotide fragment; an optimized geraniol synthase gene ObGES is integrated into the plasmid 1, and an optimized geranylgeranyl diphosphate synthase gene AgGPPS is integrated into the plasmid 1 to obtain a plasmid 3; an optimized EcGeDH is integrated into the plasmid 3 to obtain a plasmid 4; an optimized SsOYE2.6 W78Y / C113I is integrated into the plasmid 2, and an optimized ZmSHC F486C is integrated into the plasmid 2 to obtain a plasmid 5; the plasmids 4 and 5 are introduced into escherichia coli to obtain the recombinant escherichia coli for producing isopulegol; and the recombinant escherichia coli of the application can obtain isopulegol after fermentation.

The present invention relates to a method of generating antibody payload conjugates in which protein asparaginyl ligases (PALs) and glutaminyl cyclase (QC) are used to conjugate payloads to antibodies. In a specific embodiment, it exemplified trastuzumab comprising a GGGSNQL at the C-terminus of the light chain that is conjugated to MMAE comprising the Gl motif.

This application relates to the field of drug synthesis technology and provides a method for preparing levofloxacin. The method includes first mixing N,N-dimethylaminoacrylate, triethylamine, and toluene, then adding 2,3,4,5-tetrafluorobenzoyl fluoride dropwise and reacting it with L-2-aminopropanol. After post-treatment, a toluene solution of the amine is obtained. Next, using N,N-dimethylformamide or toluene as a solvent, a cyclization reaction is carried out with differentiated feeding methods and temperature control. The product is purified by hot slurrying with a non-alcoholic organic solvent or a saturated alcohol solution of the levofloxacin cyclase. Finally, the product is purified by acidic hydrolysis, piperacillin reaction, and dimethyl sulfoxide to obtain high-purity levofloxacin. This application optimizes solvent selection and process integration, shortens reaction time, improves product yield and purity, reduces waste emissions, allows for resource utilization of byproducts, and features a simple and easily industrialized process suitable for large-scale production.

This invention discloses a directed evolution strategy for SsDMS, a type II sesquiterpene cyclase derived from *Streptomyces showdoensis*, based on alanine scanning, and its applications. The invention describes several key mutant sites in SsDMS capable of catalyzing the generation of novel dried sesquiterpene compounds, including substitutions at positions 208, 248, 249, 497, and 505. This invention also discloses a highly efficient *E. coli* cell factory applied to the heterologous expression of SsDMS mutants and the efficient production of novel dried sesquiterpene compounds, further yielding structurally novel dried sesquiterpene compounds. This invention achieves the efficient production of dried sesquiterpene compounds using SsDMS and its mutants. Its modification strategy has broad applicability, providing important enzymatic resources for the biosynthesis of novel terpenoids and offering more options for the discovery of drug lead compounds.

The invention belongs to the field of biological medicine, and particularly relates to a piperidine-2, 6-diketone compound, a pharmaceutical composition and a preparation method and application of the piperidine-2, 6-diketone compound. The piperidine-2, 6-diketone compound provided by the invention can be used for preparing a glutamine cyclase (sQC / gQC) inhibitor and an IKZF1 / 3 or VAV1 targeted degradation agent, provides a new medication choice for clinical treatment of diseases (such as Alzheimer's disease, inflammation, immune related diseases and tumors) which are related to abnormal activity of glutamine cyclase and are abnormally expressed by IKZF1 / 3 or VAV1, and has a broad application prospect. The application prospect is good.

An inhalable pharmaceutical composition containing a soluble guanylate cyclase (SGC) receptor agonist, and a use thereof. The present invention can reduce the hypotensive side effects caused during administration, allows blood pressure to rapidly return to a normal level after administration, and enables the SGC receptor agonist to enter blood more quickly, improving pharmacokinetic parameters such as Tmax; and under specific formulations and instrument combinations, a pulmonary deposition rate can reach 40% or above.

The invention firstly provides an enzyme system for improving the yield of astaxanthin. The enzyme system comprises beta-carotene hydroxylase crtZ, beta-carotene ketolase crtW and lycopene cyclase crtY which are found by the inventor and have remarkably improved conversion rate. The beta-carotene hydroxylase crtZ has an amino acid sequence as shown in SEQ ID NO: 2, the beta-carotene ketolase crtW has an amino acid sequence as shown in SEQ ID NO: 3, and the lycopene cyclase crtY has an amino acid sequence as shown in SEQ ID NO: 1. On the basis, coding genes of the beta-carotene hydroxylase crtZ, the beta-carotene ketolase crtW and the lycopene cyclase crtY are over-expressed in a basic strain for producing the lycopene, and an escherichia coli recombinant strain for producing the astaxanthin at high yield is constructed. When the recombinant escherichia coli is used for producing astaxanthin through fermentation, the yield and the conversion rate of the astaxanthin are obviously improved; according to the present invention, glycerol is adopted as a substrate, and fermentation is performed in a 5 L fermentation tank for 60 h to obtain 1.54 g / L of astaxanthin (1.18 g / L in the prior art), such that the technical problem of low yield of astaxanthin produced through microbial fermentation in the prior art is solved, the foundation is laid for the industrial production of astaxanthin, and wide application prospects and huge market values are provided.