195 results about "G protein" patented technology

The present invention provides a rabies virus G protein antigen epitope targeting completely human monoclonal antibody and applications thereof, the completely human monoclonal antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region has three complementary determining region amino acid sequences: GDISSSCFY, IHYSGST and ARHRRGYCYDSEKGGTNWFDP, and the light chain variable region has three complementary determining region amino acid sequences: GDISSSCFY, IHYSGST and ARHRRGYCYDSEKGGTNWFDP. The amino acid sequences of the three complementary determining regions of the light chain variable region are respectively as follows: QGISND, ATS and LQDYEFPLT. The fully human monoclonal antibody has efficient and broad-spectrum anti-rabies virus neutralizing activity, is high in expression, fully human-derived and good in stability, and can be used for preparing rabies virus detection products or drugs for preventing and treating rabies.

This invention discloses a protein and gene related to resistance to neonicotinoid acetylcholine receptor competitive regulator insecticides in peach aphids, and their applications. It relates to the field of screening technology for neonicotinoid acetylcholine receptor competitive regulator insecticides in peach aphids. This invention obtains and clarifies an MpeABCC_4G protein and its encoding gene that is closely related to the resistance of peach aphids to neonicotinoid acetylcholine receptor competitive regulator insecticides. By knocking down the expression of MpeABCC_4G in resistant peach aphids using RNAi technology, the control efficacy of neonicotinoid acetylcholine receptor competitive regulator insecticides is significantly improved.

The present disclosure relates to compounds useful as proton activated G protein coupled receptor modulators and pharmaceutical compositions comprising the compounds. The present disclosure also relates to methods of using such compounds and pharmaceutical compositions to treat and / or prevent diseases, disorders or conditions mediated by proton activated G protein coupled receptors.

The invention discloses a paralichthys olivaceus rhabdovirus G protein tandem antigen epitope peptide and application thereof, and belongs to the field of fish molecular immunology. The amino acid sequence of the tandem antigen epitope peptide is shown as SEQ ID NO: 1. The preparation method comprises the following steps: (1) firstly, analyzing structural characteristics of HIRRV-G protein, predicting B cell antigen epitopes of the HIRRV-G protein, screening the antigen epitopes with advantages on the basis of a prediction result, and synthesizing the antigen epitopes; (2) screening a candidate peptide fragment with high affinity through an enzyme-linked immunosorbent assay; and (3) sequentially connecting the high-affinity peptide fragment sequences meeting the requirements by using a GPGPG connexon, cloning the connected sequences into a pET-28a prokaryotic expression vector, and performing induced expression to obtain the tandem antigen epitope peptide. Compared with a full-length G protein, the tandem antigen epitope peptide is smaller in molecular weight, higher in stability and higher in hydrophilicity; a large number of specific antibodies can be induced in fish bodies, and the death rate of the paralichthys olivaceus infected by viruses is remarkably reduced. The method can be used for HIRRV diagnosis detection reagent and subunit vaccine development.

Disclosed are fusion proteins (homodimers and heterodimers thereof). Fusion proteins that can bind to a protein of interest that is a G Protein-Coupled Receptor (GPCR) and to an internalizing receptor on a cell surface (transferrin receptor). Once bound, the protein of interest can be internalized and / or degraded inside a cell.

The invention discloses preparation and application of a rabies virus G protein mRNA vaccine freeze-drying preparation, and relates to the field of veterinary biological products. According to the invention, rabies virus G protein mRNA is prepared on a large scale through an in-vitro transcription technology, and an mRNA-LNP (lipid nanoparticle) delivery system is successfully constructed by adopting a microfluidic encapsulation process. Through freeze-drying protective agent formula screening (including cane sugar, trehalose and mannitol) and freeze-drying procedure parameter optimization (including pre-freezing temperature, main drying rate and secondary drying residual moisture control), the freeze-dried mRNA vaccine preparation which can stably exist under the condition of 4 DEG C is finally obtained.

The invention discloses a construction method and application of a rabies virus RNA polymerase dual-luciferase report system, and belongs to the technical field of biology. In order to solve the technical problem that a report system for detecting the RABV RNA polymerase activity needs to be developed urgently, a Firefly luciferase fragment and a vector pcDNA3.1-SRV9-M-G obtained by amplifying M protein and G protein-deleted rabies virus SRV9 strain full-length plasmid are seamlessly connected, a recombinant luciferase report plasmid is constructed, the recombinant luciferase report plasmid and an auxiliary plasmid are combined, and the recombinant luciferase RNA polymerase activity detection system is constructed. And the RABV RNA polymerase dual-luciferase report system is formed by the Renilla luciferase report plasmid and the T7 promoter plasmid, and the RABV RNA polymerase dual-luciferase report system comprises the Renilla luciferase report plasmid and the T7 promoter plasmid. The system can accurately and efficiently detect the activity of RABV polymerase, and by virtue of the function, effective antiviral targets and therapeutic drugs can be screened out in an assisted manner.

The present disclosure relates to a novel fluorogenic dimer compound, useful as a probe for detection of endogenous receptors, in particular G protein-coupled receptors. The present invention provides compositions and kits comprising such compound and methods of labeling a biomolecule, comprising the step of contacting the biomolecule with the compound of the invention.

The invention belongs to the field of medicinal chemistry, and relates to an indole allylamine amide derivative as well as a preparation method and application thereof. Functional activity screening of G protein dependent signaling pathways is carried out on all the synthesized compounds, and it is found that the new derivatives can be used for preparing beta2-adrenergic receptor allosteric antagonism regulator drugs. Trans-indole allylamine is used as a raw material, amide coupling is performed to obtain the novel indole allylamine amide derivative, and R1 is any one of phenyl, m-methylbenzene, m-methoxyphenyl, m-bromophenyl, m-chlorphenyl, m-fluorophenyl, o-methoxyphenyl, p-methoxyphenyl, naphthalene ring, oxazole, cyclohexyl, cyclopentyl, methyl, ethyl and isopropyl. A biological activity test result shows that the indole allylamine amide derivative disclosed by the invention has relatively good antagonistic activity on beta2AR and can be used for carrying out negative allosteric regulation on the functional activity of isoproterenol.

Provided are a method and system for predicting an activation potency of agonist molecules on G Protein-Coupled Receptors (GPCRs). The method includes: blindly speculating complex structures formed by binding of a ligand to an activated receptor structure and an inactivated receptor structure, respectively, via global molecular docking; extracting an initial path enabling an inactivated complex structure to be activated to an activated complex structure based on an enhanced sampling algorithm; searching for a minimum free energy path closest to the initial path by applying an automatic path optimization algorithm; calculating a free energy distribution curve along the minimum free energy path by employing umbrella sampling and determining an energy barrier height and a free energy difference before and after activation, thereby determining the activation potency of the ligand structure on the GPCRs.

The present invention provides a compound having inhibitory activity against a Mas-related G protein-coupled receptor X2. The present invention provides a compound having the following structural formula or the like, or a pharmaceutically acceptable salt thereof.

The application discloses a tandem antigen epitope peptide of G protein of Paralichthys olivaceus rhabdovirus and application thereof, and belongs to the field of fish molecular immunology. The amino acid sequence of the tandem antigen epitope peptide is shown as SEQ ID NO:1. The preparation method of the application comprises the following steps: (1) first, analyzing the structural characteristics of HIRRV-G protein and predicting B cell antigen epitopes, and synthesizing the antigen epitopes with advantages based on the prediction results; (2) then, screening candidate peptide segments with high affinity through enzyme-linked immunosorbent assay; (3) sequentially connecting the high-affinity peptide segment sequences meeting the requirements by using a GPGPG linker, and cloning the connected sequences into a pET-28a prokaryotic expression vector, so that the tandem antigen epitope peptide is obtained after induced expression. Compared with the full-length G protein, the tandem antigen epitope peptide has smaller molecular weight, stronger stability and stronger hydrophilicity; the tandem antigen epitope peptide can induce a large amount of specific antibodies in fish bodies, and significantly reduces the mortality of fish infected by the virus. The tandem antigen epitope peptide can be used for the development of HIRRV diagnostic reagents and subunit vaccines.

Provided is an anti-G protein-coupled receptor family class C group 5 member D (GPRC5D) antibody or a fragment thereof. Also provided is the use of the antibody or fragment thereof as an active ingredient for treatment of tumors or cancers. In addition, further provided is a bispecific antibody comprising the antibody or fragment thereof and aiming at GPRC5D and CD3.

A bispecific antibody targeting a G protein coupled receptor is provided. Specifically provided are bispecific antibodies, nucleic acids encoding them, vectors comprising the nucleic acids, cells comprising the vectors, pharmaceutical compositions comprising the multispecific antibodies, and uses thereof in treating subjects with related diseases.

The present invention provides neutralizing monoclonal antibodies targeting Nipah virus G protein and their uses, wherein the monoclonal antibodies can recognize Nipah virus G protein. The present invention uses NiV G protein as an antigen target, displays antigens on a ferritin nanoparticle platform to immunize mice, and screens out three monoclonal antibodies that can specifically bind to NiV G protein. Antibody epitope competition experiments found that the S1E2 and SB10 monoclonal antibodies among these three antibodies recognize new epitopes of NiV G protein that have not been reported before. In vitro neutralization experiments have demonstrated that these three antibodies have high in vitro neutralizing activity, and can neutralize both NiV-M and NiV-B strains, with the characteristics of high expression and good stability, and can be used to prepare virus detection products such as Nipah and Hendra or drugs for preventing and treating Nipah and Hendra virus diseases.

The application discloses a tetrapeptide IR4 with uric acid reducing activity, and a preparation method and application thereof, and belongs to the technical field of small molecular peptides. The amino acid sequence of the tetrapeptide IR4 is IDWR, and the tetrapeptide IR4 can be prepared by a solid-phase synthesis method and an enzymatic hydrolysis method. The tetrapeptide IR4 is identified from a porphyra haitanensis protease hydrolysate, has potential interaction with xanthine oxidase, and can reduce the uric acid content of zebrafish by 33.6% (to 5.93+ / -0.47 mu mol / g protein) at a concentration of 100 mu g / mL. Compared with an anserine (which can reduce the uric acid content of zebrafish by 25.7%), the tetrapeptide IR4 has better uric acid reducing activity. Compared with allopurinol (which can reduce the uric acid content of zebrafish to 4.61+ / -1.11 mu mol / g protein), the uric acid reducing ability of the tetrapeptide IR4 and the allopurinol has no significant difference. The tetrapeptide IR4 can be used for preparing uric acid reducing drugs and relieving hyperuricemia.

The application discloses application of a peripheral nervous system Mas-related G protein-coupled receptor D as a target point in preparation of a medicine for screening for relieving opioid tolerance. Jun The application further provides a medicine composition for regulating opioid tolerance, containing a Mas-related G protein-coupled receptor D siRNA sequence shown in SEQ ID NO. 1 or a siRNA sequence shown in SEQ ID NO. 2. The application further provides an in-situ hybridization kit for detecting expression of a Mas-related G protein-coupled receptor D gene in a dorsal root ganglion tissue of a peripheral nervous system. The application expands a new path for opioid companion diagnosis and intervention.

The present invention relates to an antibody or antibody fragment capable of binding to G protein alpha, a nucleic acid sequence encoding said antibody, a vector comprising said nucleic acid sequence, a cell comprising said vector or said nucleic acid sequence and a kit comprising: i) said antibody or antibody fragment or said composition and ii) a GTP source labeled with a member of a RET partner pair.

Disclosed are compositions that can bind to a CCR6 G Protein-Coupled Receptor (GPCR) and to a transferrin receptor on a cell surface. Once bound, the protein of interest (CCR6) can be internalized and / or degraded inside a cell.

Disclosed are monoclonal antibodies and antigen binding fragments thereof that specifically bind to Nipah virus (NiV) F or G protein. In several examples, the antibodies and antigen binding fragments are cross-reactive with other Henipavirus F or G proteins, such as Hendra virus (HeV) F or G proteins. Also disclosed is the use of these antibodies and antigen binding fragments for inhibiting a Henipavirus infection, such as a NiV and / or HeV infection. In addition, disclosed are methods for detecting Henipavirus, such as NiV or HeV in a biological sample, using the disclosed antibodies and antigen binding fragments.

Provided herein are methods and uses of combination therapies involving a GPRC5D-targeted cell therapy comprising a chimeric antigen receptor (CAR) containing an extracellular antigen binding domain that binds to G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D) and a combination agent, e.g., a bispecific antibody, for treating a subject having a cancer, such as multiple myeloma, as well as related methods, uses, and articles of manufacture.

The invention discloses application of a peripheral nervous system Mas related G protein coupled receptor D as a target spot in preparing and screening a medicine for relieving opioid medicine tolerance. The invention also provides a pharmaceutical composition for regulating and controlling the tolerance of the opioid drugs. The pharmaceutical composition contains a Mas related G protein coupled receptor D siRNA sequence as shown in SEQ ID NO. 1 or a Jun siRNA sequence as shown in SEQ ID NO. 2. The invention also provides an in-situ hybridization kit for detecting the expression of the Mas related G protein coupled receptor D gene in the dorsal root ganglion tissue of the peripheral nervous system. According to the invention, a new path for accompanying diagnosis and intervention of opioid drugs is expanded.

In the present invention, there is discovered a novel mRNA vaccine for preventing respiratory syncytial virus (RSV) infections, the mRNA vaccine being superior in terms of immunogenicity and pharmacological efficacy compared with RSV FG chimeric protein vaccines each comprising RSV F and G proteins and mRNA vaccines which have been produced on the basis of Japanese Patent No. 7253034 (Patent Document 7). In the present invention, an RSV FG chimeric mRNA vaccine is produced by inserting a highly conserved domain of the RSV G protein into a basic skeleton that is formed by linking a transmembrane region to an RSV F protein ectodomain. As a result of performing evaluation on immunogenicity and pharmacological efficacy, it has been confirmed that the immunogenicity and pharmacological efficacy of the RSV FG chimeric mRNA vaccine of the present invention are superior compared with those of the RSV FG chimeric protein vaccines and mRNA vaccines which have been produced on the basis of Patent Document 7.

This invention provides RNAi agents, such as dsRNA agents, that target the G protein-coupled receptor 75 (GPR75) gene. It also provides methods for using such RNAi agents to inhibit the expression of the GPR75 gene in a subject, and methods for treating or preventing GPR75-related diseases such as weight disorders, e.g., obesity. [Solution] A double-stranded ribonucleic acid (dsRNA) agent for inhibiting the expression of the GPR75 gene in cells is provided, comprising a sense strand and an antisense strand that form a double-stranded region, wherein the antisense strand comprises a region complementary to a portion of the mRNA encoding the GPR75 gene, each strand is independently 14 to 30 nucleotides long, and the sense strand or antisense strand is conjugated to one or more lipophilic portions.

Provided is a use of a G protein-coupled receptor kinase 2 (GRK2) degradation compound in lowering blood glucose, stimulating or increasing insulin secretion, or preventing or treating a disease or disorder related thereto. Specifically, provided is a use of a compound represented by Formula (1) that degrades G protein-coupled receptor kinase 2 (GRK2) or a pharmaceutically acceptable salt, an isomer, an isotope, a prodrug, a solvate, or a polymorph thereof or a pharmaceutical composition comprising the same in lowering blood glucose, stimulating or increasing insulin secretion, or preventing or treating a disease or disorder that is ameliorable by lowering blood glucose, for example a pre-diabetic condition, a diabetes, or a complication related to a pre-diabetic condition or a diabetes in a subject in need thereof.

The application discloses a pentapeptide IK5 with uric acid reducing activity as well as a preparation method and application thereof, and belongs to the technical field of small molecular peptides. The amino acid sequence of the pentapeptide IK5 is ITGYK, and the pentapeptide IK5 can be prepared by a solid-phase synthesis method and an enzymolysis method. The pentapeptide IK5 is identified from a protease enzymolysis liquid of a fine weak red winged seaweed, has potential interaction with xanthine oxidase, and can reduce the uric acid content of zebrafish by 44.4% (to 5.93+ / -0.47 mu mol / g protein) at a concentration of 100 mu g / mL. Compared with ananeine (which can reduce the uric acid content of zebrafish by 25.7%), the pentapeptide IK5 has better uric acid reducing activity. Compared with allopurinol (which can reduce the uric acid content of zebrafish to 4.61+ / -1.11 mu mol / g protein), the uric acid reducing ability of the pentapeptide IK5 and the allopurinol has no significant difference. The pentapeptide IK5 can be used for preparing uric acid reducing drugs and relieving hyperuricemia.

The present invention concerns a new gene therapy approach to increase light-sensitivity in degenerating cones in advanced stages of rod-cone dystrophy (RCD) mediated by G-protein-gated-K+ channel (GIRK), in particular GIRK1 F137S, activated by G proteins recruited by cone opsin expressed in degenerating cones.

This invention discloses nanobodies against rabies virus G protein and their applications, belonging to the field of nanobody technology. The nanobodies are antibody 11G6, antibody 9F7, or antibody 9A3; the amino acid sequence of antibody 11G6 is shown in SEQ ID NO. 8; the amino acid sequence of antibody 9F7 is shown in SEQ ID NO. 13; and the amino acid sequence of antibody 9A3 is shown in SEQ ID NO. 18. This invention uses phage display technology to screen for nanobodies with high affinity and high neutralizing activity. Based on this, this invention utilizes the advantage of the small size of nanobodies and verifies their unique ability to cross the blood-brain barrier (BBB) ​​through Transwell experiments, overcoming the limitation that large molecules such as antibodies and drugs cannot cross the BBB to enter the brain. This invention provides a new drug option for the treatment of rabies virus and has significant clinical implications.

The present invention discloses an application and a kit for differential histoproteins and / or metabolites of pigmented villonodular synovitis; the differential histoproteins include at least one of the following proteins: TNFSF11, cathepsin K, and adhesion G protein-coupled receptor E5; the differential metabolites include at least one of the following products: 13-hydroxyperoxylinoleic acid and octadecadienoic acid; the present invention provides a new screening marker for pigmented villonodular synovitis (PVNS) through proteomics and metabolomics, which can achieve effective screening for pigmented villonodular synovitis; the obtained screening marker is used in a screening kit, which only needs synovial fluid as a test sample, can quickly perform screening and detection, and has the advantages of high efficiency and simple detection.

The invention relates to engineered exosomes and methods of making the same. The engineered exosome comprises an Arc protein and a VSV-G protein. After the Arc protein and the VSV-G protein are increased in the exosome, the loading capacity of the load in the exosome is improved, so that the load is further enriched in the exosome, and the effective release of the load in uptake cells is promoted. On the basis of adding Arc protein and VSV-G protein in the exosome, a targeting group and / or a macrophage escape group are added to realize the functions of nucleic acid loading, cell targeting and macrophage escape, and the effect of taking in a load in a cell is integrally improved.