281 results about "G protein" patented technology

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 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 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.

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.

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 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.

The invention discloses a rabies vaccine and a preparation method thereof. The rabies virus G truncated mutant protein comprises a circular RNA (Ribonucleic Acid) molecule for coding rabies virus G truncated mutant protein and a pharmaceutically acceptable carrier, wherein the amino acid sequence of the rabies virus G truncated mutant protein is as shown in SEQ ID No.13 or a degenerate sequence thereof, and the nucleotide sequence is as shown in SEQ ID No.14 or a degenerate sequence thereof; the nucleotide sequence of the circular RNA molecule is as shown in SEQ ID No. 20. At present, RNA vaccines for resisting rabies virus infection are not applied in batches, the optimized rabies virus G protein circular RNA molecules and the optimized lipid nanoparticles are used for preparing the vaccines, and the process can be industrially amplified. The animal can be induced to generate a high-level neutralizing antibody and a more lasting drug effect only by injecting a low-dose circular RNA vaccine (16 [mu] g / vaccine) once, the vaccine is good in safety and stability, and a basis is provided for industrial preparation and application of the vaccine.

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.

Provided herein are compounds that inhibit a binding interaction between a β integrin and a G protein subunit, as well as compositions, e.g., pharmaceutical compositions, comprising the same, and related kits. In some embodiments, the compound is an antibody or antibody analog, and, in other embodiments, the compound is a peptide or peptide analog. Also provided are methods of using the compounds, including methods of treating or preventing a medical condition, such as stroke, heart attack, cancer, or inflammation.

The present invention relates to a viral strain derived from a human metapneumovirus (hMPV) strain having a genomic sequence represented by sequence SEQ ID NO: 1 wherein the genomic sequence comprises the following genetic modifications: (i) inactivating an endogenous gene encoding an SH protein and / or a G protein, and (ii) the presence of an exogenous sequence encoding at least one extracellular domain of an F protein of a human respiratory syncytial virus (hRSV), the domain is of a wild type or mutant.

The invention discloses a rabies mRNA vaccine and application thereof. The rabies mRNA vaccine takes mRNA of G protein of rabies virus as an active ingredient. The mRNA comprises a coding sequence of a G protein of the rabies virus, and the coding sequence is selected from any one of the following sequences: (1) the G protein comprises an amino acid sequence as shown in SEQ ID NO: 1, and the coding sequence comprises a nucleic acid sequence as shown in any one of SEQ ID NO: 10-14 and 17; and (2) the G protein comprises an amino acid sequence as shown in SEQ ID NO: 8. Compared with the traditional inactivated vaccine, the vaccine provided by the invention has stronger immunogenicity, can stimulate stronger humoral immune response, and has better protection effect.

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.