378 results about "G protein" patented technology

The present application relates to the technical field of drug screening, and in particular to a method and system for enhancing the ability of a large language model to answer questions of a specific field. The method comprises the following steps: using a large language model to extract a relation triple from a data set, wherein the data set comprises structured data and unstructured data; on the basis of the relation triple, constructing a knowledge graph of G protein coupled receptors (GPCRs), and storing the knowledge graph in a form of a graph database, wherein the knowledge graph comprises a GPCR entity and a relation thereof; using a pre-trained large language model to search the graph database for related information of a specific field to obtain prompt information, wherein the specific field is the field of GPCRs; and on the basis of the prompt information and the pre-trained large language model, obtaining an answer result, wherein the answer result is returned to a user by the pre-trained large language model. In the present application, by constructing a knowledge graph, the large language model is endowed with accurate and real-time field knowledge of GPCRs, and the ability of the large language model to answer questions of the field of GPCRs is enhanced.

The invention discloses a G protein biased apelin-13 polypeptide mutant and an application of the G protein biased apelin-13 polypeptide mutant. The invention is based on polypeptide design with a reasonable structure. Two amino acids M11 and F13 which are combined on'twin hotspots' on a locked polypeptide ligand are mutated or modified to regulate a receptor to adopt a G protein biased conformation. Functional verification is carried out on part of the designed polypeptides, the result shows that the polypeptides designed based on the structure conform to expectation and can block or retain weak beta-arrest activation capacity, and the verification result of part of the polypeptides can also be popularized to other polypeptides.

The invention belongs to the technical field of monoclonal antibody preparation, and particularly relates to a human-mouse chimeric monoclonal antibody for resisting human G protein-coupled receptor family member 1 (LGI1 protein) as well as a product and application of the human-mouse chimeric monoclonal antibody. The variable regions of the heavy chain and the light chain of the human-mouse chimeric monoclonal antibody of the anti-human LGI1 protein come from mice, and the constant regions of the heavy chain and the light chain of the human-mouse chimeric monoclonal antibody are human antibody constant regions, so that the human-mouse chimeric monoclonal antibody can replace the function of serum to a certain extent on the basis of retaining parent activity to the greatest extent; meanwhile, the technical problems that the Fc region of the existing anti-human LGI1 protein monoclonal antibody cannot react with the anti-human IgG antibody, the sensitivity difference among multiple batches of antibodies is large, and batch production cannot be realized can be solved. Furthermore, the human-mouse chimeric monoclonal antibody of the anti-human LGI1 protein can be used for detecting the LGI1 protein and an LGI1 autoantibody.

The invention discloses a neurotoxicity-free recombinant live virus vector rabies vaccine, which is prepared by replacing G protein of vesicular stomatitis virus with G protein of HEP-Flury rabies virus strain or G protein mutant of HEP-Flury rabies virus strain, and saving recombinant virus VSV-HEP-Flury by using a reverse genetic manipulation technology. The recombinant live virus vector rabies vaccine has no neurotoxicity after being inoculated. The method is free of neurotoxicity, high in safety, simple in inoculation procedure, good in immune effect and high in productivity.

The invention relates to the technical field of biological medicines, in particular to a rabies virus G protein mutant as well as a preparation method and application thereof. The rabies virus G protein mutant is obtained by carrying out point mutation on an extracellular domain of G protein, the mutant realizes soluble expression of the extracellular domain of the G protein, can induce generation of a high-titer neutralizing antibody, and has more excellent cellular immunity and antibody immune response compared with commercial human rabies vaccines and canine rabies vaccines; the inoculation frequency is expected to be reduced, the immune procedure is shortened, and the immune dosage is reduced.

The present disclosure relates to bicyclic heterocycles of Formula (I), and pharmaceutical compositions of the same, that are modulators, antagonists, or inhibitors of the G protein-coupled receptor MRGPRX2 and are useful in the treatment of MRGPRX2 dependent conditions such as inflammatory diseases.

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.

Polypeptides comprising an extracellular domain of rabies virus G protein are provided. The rabies virus G protein extracellular domain may have a deletion of the fusion ring domain. Further provided are nanoparticle vaccines for rabies virus. Further provided are pharmaceutical compositions, methods of making, and methods of using, such as immunizing a subject to produce a protective immune response against rabies virus.

The invention discloses a transformation method and application of a G protein coupled receptor, and belongs to the technical field of protein engineering. In order to improve the molecular weight of membrane protein, enable the enlarged part of the membrane protein and the original membrane protein to form a relatively rigid structure and further meet the structural analysis requirement of a cryoelectron microscope, the invention provides a method for transforming a G protein coupled receptor. The method comprises the following steps: co-expressing fusion protein GPCR (Glycine Polymerase Chain Reaction)-GFP10-11 and GFP1-9 fragments formed by GPCR and GFP10-11 fragments in a eukaryotic cell expression system, and adding GFP-clamp in the purification process; one amino acid at the specific site of GPCR is mutated into cysteine, glutamic acid at the 186th position of the amino acid sequence of GFP-clamp is mutated into cysteine, and a disulfide bond is formed between the amino acid and glutamic acid. The molecular weight of the modified G protein coupled receptor obtained by using the method can be increased to 85 kD or above, and the rigidity of the whole compound space structure is relatively strong, so that the modified G protein coupled receptor can be used for structural analysis of a cryoelectron microscope.

The invention relates to a novel rabies virus nucleocapsid nanostructure vaccine and a construction method thereof, and belongs to the field of biomedicine.The nanostructure vaccine is characterized in that mRNA capable of efficiently expressing rabies virus G protein and recombinant rabies virus N protein expressed by escherichia coli are combined to form an NLS structure serving as a vaccine antigen component; and then wrapping with a lipid component. The vaccine constructed by the invention can form G antigen and N antigen integrated immunogen signal stimulation, so that specific immunity can form an effective reaction in humoral immunity and cellular immunity. In a protective test of challenge, the vaccine can achieve a 100% protection effect on mice.

The present disclosure relates to bicyclic heterocycles of Formula (I), and pharmaceutical compositions of the same, that are modulators, antagonists, or inhibitors of the G protein-coupled receptor MRGPRX2 and are useful in the treatment of MRGPRX2 dependent conditions such as inflammatory diseases.

The present application relates to a chimeric antigen receptor, comprising a first antigen binding domain and a second antigen binding domain. The first antigen binding domain targets a G protein-coupled receptor class C group 5 member D (GPRC5D) protein, and the second antigen binding domain targets the GPRC5D protein. The present application further provides a cell comprising the chimeric antigen receptor and use thereof.

The invention belongs to the field of medicinal chemistry, and particularly discloses application of oxime cholic acid analogues as TGR5 allosteric agonists. The preparation method comprises the following steps: by taking cholic acid as a raw material, obtaining cholic acid intermediates of which the 12th site or the 7th site and the 12th site are oximes through a series of reactions, and then carrying out a series of modification on the 24th site and oximes of the intermediates to obtain the cholic acid analogue as shown in a formula 1 or a formula 2. According to the invention, a GloSensor cAMP accumulation experiment is adopted to test the functional activity and allosteric regulation mechanism of all compounds on TGR5 on a G protein dependent signal channel. Pharmacological results show that all the synthesized target compounds have relatively good agonist activity on TGR5, and can positively allosteric regulate the functional activity of chenodeoxycholic acid CDCA, that is, the target compounds disclosed by the invention are all TGR5 positive allosteric modulators or allosteric agonists. # imgabs0 # imgabs1 #

The invention belongs to the technical field of biological medicine, and discloses an application of recombinant protein in preparation of a snakehead vesicular virus vaccine. A G protein of a snakehead vesicular virus (SHVV) is taken as an antigen for the vaccine, recombinant escherichia coli BL21 (pET32a-G) capable of expressing the protein is constructed by utilizing a genetic engineering technical means, recombinant protein rG is obtained through induced expression, and the nano-carrier vaccine (BNC-rG vaccine) of the snakehead vesicular virus is prepared by taking bacterial nano-cellulose as a carrier. According to the BNC-rG vaccine provided by the invention, immune protection against SHVV can be realized through immersion immunization, the specific antibody level is remarkably improved, the relative protection rate of snakehead reaches 80.00% after snakehead is infected with SHVV after immersion immunization for 4 weeks, and the immune protection effect is remarkable.

The present application relates to a chimeric antigen receptor, comprising a first antigen binding domain and a second antigen binding domain. The first antigen binding domain targets a G protein-coupled receptor class C group 5 member D (GPRC5D) protein, and the second antigen binding domain targets the GPRC5D protein. The present application further provides a cell comprising the chimeric antigen receptor and use thereof.

In aspects, the present disclosure provides a recombinant protein comprising (a) a rhabdoviral G glycoprotein or a functional fragment or derivative thereof, wherein the rhabdoviral G glycoprotein or functional fragment or derivative thereof is capable of binding to or interacting with low density lipoprotein receptor (LDLR); and (b) a cysteine rich region, wherein the cysteine rich region comprises a cysteine rich domain of LDLR, and wherein the cysteine rich region is capable of binding to or interacting with rhabdoviral G glycoprotein or a functional fragment or derivative thereof; wherein the cysteine rich region is covalently bonded to the rhabdoviral G glycoprotein or functional fragment or derivative thereof.

Provided herein are lipid particles, such as lenti viral particles, that incorporate or are pseudotyped with a variant Nipah Virus G (NiV-G) envelope glycoprotein, and in some aspects also a fusion (F) protein such as a NiV-F protein or a biologically active portion or variant thereof. Also provided are polynucleotides encoding the variant NiV-G and producer cells for preparation of the lipid particles, such as lentiviral particles, containing the variant NiV-G proteins, as well as methods for preparing and using the lipid particles, such as lentiviral particles.

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.

Provided are an antagonist of the MAS-related G protein-coupled receptor X2 (MRGPRX2) and the use thereof. The MRGPRX2 antagonist has a structure of formula (I).

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 belongs to the field of medicinal chemistry, and relates to an indole acrylic acid 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 synthesized compounds, and it is found that the new derivatives can be used as allosteric antagonism regulators of beta2-adrenergic receptors. Trans-indole acrylic acid with different substituent groups is used as a raw material, amide coupling is performed to obtain the novel indole acrylic acid amide derivative, and R1 is a hydrogen atom, a halogen atom, a methyl group or a methoxyl group; r2 is any one of phenyl, m-bromophenyl, m-chlorphenyl, m-fluorophenyl, m-cyanophenyl, m-methoxyphenyl, cyclohexyl and piperidyl. A biological activity test result shows that the indole acrylic acid 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.

The present invention relates to the technical field of biomedicine. Provided are a rabies virus G protein mutant, and a preparation method therefor and the use thereof. The rabies virus G protein mutant is obtained by means of a site mutation on the extracellular domain of a G protein. For the mutant, soluble expression of the extracellular domain of the G protein is realized, and the mutant can induce the generation of a neutralizing antibody with a high titer. Compared with commercial rabies vaccines for human and rabies vaccines for dogs, the mutant has better cell immune and antibody immune responses. The mutant is expected to reduce the inoculation frequency, shorten the immunizing procedure, and decrease the immunizing dose.

Provided is an approach which can express and function a G protein-coupled receptor (GPCR). The present invention provides a method for expressing a GPCR polypeptide, comprising expressing in a cell a GPCR polypeptide consisting of an amino acid sequence obtained by, in an amino acid sequence of a GPCR of interest (provided that an olfactory receptor is excluded), altering at least one amino acid residue different from that in a consensus amino acid sequence to an amino acid residue at a position corresponding thereto in the consensus amino acid sequence, wherein the consensus amino acid sequence is an amino acid sequence derived by alignment of the amino acid sequence of the GPCR of interest and amino acid sequences of GPCRs encoded by orthologs of the GPCR of interest in vertebrates.

The present disclosure relates to bicyclic heterocycles of Formula (I), and pharmaceutical compositions of the same, that are modulators, antagonists, or inhibitors of the G protein-coupled receptor MRGPRX2 and are useful in the treatment of MRGPRX2 dependent conditions such as inflammatory diseases.

The invention discloses a rice RGB1 gene mutant mRGB1 and application thereof, and relates to the technical field of plant genetic engineering, a gene editing technology is utilized, a rice G protein beta subunit coding gene (RGB1, LOCOs03g46650) N-terminal structural domain coding region is targeted, three and six basic groups are deleted from a first exon and a second exon respectively, the mutant is named as mRGB1, the mutation causes plant dwarfing, upright and dense ears, and the rice RGB1 gene mutant mRGB1 has the advantages of high yield and high yield. The seeds become small, and new gene resources can be provided for genetic improvement.

The present disclosure relates to bicyclic heterocycles of Formula (I), and pharmaceutical compositions of the same, that are modulators, antagonists, or inhibitors of the G protein-coupled receptor MRGPRX2 and are useful in the treatment of MRGPRX2 dependent conditions such as inflammatory diseases.

Provided are iPSCs and derivative cells thereof expressing multi-transmembrane domain chimeric antigen receptors utilizing G protein-coupled receptor (GPCR) scaffolds, and uses of the iPSCs or the derivative cells to express a GPCR chimeric antigen receptor (CAR) for allogenic cell therapy.

The invention belongs to the technical field of medicine and biology, and particularly relates to a vaccine for preventing and / or treating respiratory syncytial virus. Respiratory syncytial virus Pre F protein is selected as a skeleton, and the C end of the skeleton is connected with a G protein CCD part fragment. According to the invention, double neutralizing antibodies of RSV preF protein and G protein can be generated at the same time, and double effects of preventing viruses from infecting a host and preventing residual viruses from spreading again are achieved. Further, different adjuvants are utilized to improve humoral immune response and reduce vaccine enhanced pathological injury (VED) at the same time. Therefore, the invention has practical value in preventing or treating respiratory syncytial disease virus infection.

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.