137 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.

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 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.

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 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.

An RSV virus-like particle which includes a chimeric protein that includes a core consisting of an influenza M1 protein, an RSV-derived preF protein, an RSV-derived G protein or part of G protein displayed on the surface of the core, can exhibit excellent effects in terms of inhibiting RSV virus infection and inhibiting the inflammatory response of the lungs.

The present invention relates to a vaccine composition comprising a recombinant Nipah virus protein. The vaccine composition according to the present invention not only exhibits excellent immunogenicity against both the G protein and the F protein of Nipah virus, but also exhibits immunogenicity against the G protein and the F protein of Hendra virus, and thus can be used as a universal vaccine against Henipavirus. In addition, the vaccine composition has the characteristic of inducing cell-mediated immune responses, and therefore can be provided as a formulation for enhancing specific immune responses to an administered drug such as an adjuvant or a vaccine.

The present disclosure relates to compounds useful as modulators of proton-activated G protein-coupled receptors, and pharmaceutical compositions comprising same. The present disclosure also relates to methods of using such compounds and pharmaceutical compositions for the treatment and / or prevention of diseases, disorders or conditions mediated by proton-activated G pro-tein-coupled receptors.

The invention discloses an anti-rabies virus G protein nano antibody and application thereof, and belongs to the technical field of nano antibodies. The nano antibody is an antibody 11G6, an antibody 9F7 or an antibody 9A3; the amino acid sequence of the antibody 11G6 is as shown in SEQ ID NO. 8; the amino acid sequence of the antibody 9F7 is as shown in SEQ ID NO. 13; the amino acid sequence of the antibody 9A3 is as shown in SEQ ID NO. 18. According to the invention, the nano antibody with high affinity and high neutralizing activity is screened by a phage display technology. On the basis, the advantage that the size of the nano antibody is small is utilized, the unique ability of the nano antibody to penetrate through the BBB is verified through a Transwell experiment, and the defect that macromolecules such as antibodies and drugs cannot penetrate through the BBB to enter the brain is overcome. The invention provides a new drug choice for the treatment of rabies virus, and has important clinical significance.

Provided are an engineered G protein-coupled receptor, a complex comprising the engineered G protein-coupled receptor, and uses thereof. The modified G protein coupled receptor sequentially comprises an N terminal, a first transmembrane region, a first intracellular ring, a second transmembrane region, a first extracellular ring, a third transmembrane region, a second intracellular ring, a fourth transmembrane region, a second extracellular ring, a fifth transmembrane region, a third intracellular ring, a sixth transmembrane region, a third extracellular ring, a seventh transmembrane region and a C terminal from an N terminal to a C terminal, wherein at least a portion of the first intracellular loop, the second intracellular loop and / or the third intracellular loop is replaced with an optional first linker, a first portion of a fluorescent protein and an optional second linker, and wherein the first linker and the second linker independently comprise one or more amino acids.

The invention discloses an anti-rabies virus G protein monoclonal antibody, a detection reagent and application of the anti-rabies virus G protein monoclonal antibody and the detection reagent. The anti-rabies virus G protein monoclonal antibody comprises a heavy chain variable region and a light chain variable region, the amino acid sequence of the heavy chain variable region is as shown in SEQ ID No. 1; the amino acid sequence of the light chain variable region is as shown in SEQ ID No.2. The monoclonal antibody provided by the invention has high affinity and detection sensitivity to rabies virus G protein, and lays a foundation for research, development and popularization of colloidal gold test strips and fluorescence immunoassay test strips.

The invention discloses a label-free screening method and application of an FPR1 bias agonist screened by the label-free screening method to acute lung injury. According to the invention, Epic label-free screening is combined with calcium flow screening, such that a preliminarily screened FPR1 agonist is obtained; the FPR1 biased agonist is obtained through a G protein dissociation experiment and a beta-arrest collection experiment; the FRP1 antagonist is obtained through screening of a known FPR1 agonist. The FPR1 bias agonist kinetin nucleoside is obtained for the first time, and by detecting the superoxide inhibiting, cast-off cell inhibiting and MPO inhibiting functions of the bias agonist KR, it is proved that the bias agonist KR has the function of treating acute lung injury. The invention discovers that the kinetin nucleoside has the effect of treating the acute lung injury for the first time.

Provided are a GPR65 small molecule regulator, a preparation method therefor, and an application, relating to the field of medicinal chemistry. The structure of the pyrimidine derivative is as shown in formula (I). The compound of the present invention has excellent antagonistic activity against human G protein-coupled receptor 65, and has broad application prospects in the preparation of anti-epileptic and anti-tumor drugs.