420 results about "Mutant protein" patented technology

The present disclosure provides compounds having activity as inhibitors of the G12C mutant KRAS protein, pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to lung cancer, pancreatic cancer, colorectal cancer, and solid tumors. In particular, the disclosure provides compounds of Formula (I):, and pharmaceutically acceptable salts thereof, wherein the substituents are as described.

The present application relates to a novel tricyclic derivative compound as a KRAS mutant protein inhibitor, and use thereof. The compound according to one embodiment of the present application inhibits the activity of a KRAS mutant protein and thus can be used in the prevention or treatment of diseases induced by KRAS mutation.

The present invention relates to the technical field of biomedicine. Specifically provided are a respiratory syncytial virus (RSV) Pre-F recombinant protein nanoparticle vaccine and a preparation method therefor. By performing amino acid mutation on an RSV Pre-F protein, and performing fusion expression on the mutated Pre-F protein and ferritin particles in eukaryotic cells, PreF-Ferritin fusion protein nanoparticles, in which eight Pre-F protein trimers are densely displayed on the surface of each ferritin particle, are obtained. By stabilizing and exposing antigen epitopes required to be displayed and disrupting or masking unrequired antigen epitopes, the PreF-Ferritin fusion protein nanoparticles effectively improve the immunogenicity and the production stability of the antigen. Experiments show that: when the PreF-Ferritin fusion protein is injected into mice, high-titer protective sera can be acquired, and the mice sera can yield relatively high neutralizing titers against RSV.

The present invention relates to 4-1BB ligand (4-BBL) extracellular domain (ECD) muteins having reduce affinity for its cognate receptor 4-1BB. The 4-1BBL ECD muteins can be present in homo- or heterotrimeric fusion protein comprising three 4-1BBL ECD monomers. The invention further relates conjugates of such the 4-BBL ECD muteins with a heterologous moiety, such as an antigen binding protein. The antigen-binding regions comprised in the antigen binding protein in the conjugates preferably are specific for a tumor-associated antigen (TAA). In addition to a 4-BBL ECD mutein, the conjugates can comprise further NK cell-activating cytokines, such an IL-21 receptor agonist. The conjugates can further comprise an antigen-binding region that has affinity for a surface antigen expressed on NK cells, e.g. CD16A. Alternatively, the conjugates can further comprise an antigen-binding region that specifically binds an epitope of a γδ TCR. The conjugates of the invention specifically redirect and activate NK cells or γδ T cells to lyse targeted tumor cells. The invention further relates to the use of the 4-BBL ECD muteins and conjugates thereof in the treatment of cancer, preferably a cancer expressing the TAA.

This invention provides a nitrile hydrolase mutant and its application in the synthesis of p-cyanobenzoic acid. The invention provides a nitrile hydrolase mutant that enhances the catalytic activity for the synthesis of p-cyanobenzoic acid. The mutant protein is a non-natural protein, and it exhibits significantly enhanced activity in catalyzing the conversion of terephthalonitrile to p-cyanobenzoic acid. Furthermore, the mutant protein contains mutations in two or more core amino acids related to the enzyme's catalytic activity in the wild-type nitrile hydrolase. The nitrile hydrolase mutant of this invention can significantly improve the yield of the synthesized product catalyzed by the nitrile hydrolase.

The application discloses efficient expression of Aspergillus oryzae beta-galactoside enzyme mutant and application thereof in dairy products, and belongs to the technical fields of enzyme engineering and dairy product processing, and particularly relates to efficient expression of Aspergillus oryzae beta-galactoside enzyme mutant and application thereof in dairy products.The mutant protein can be as follows: A1) a protein with an amino acid sequence of SEQ ID No.2; A2) a fusion protein with the same function obtained by connecting a label to the N terminal and / or C terminal of A1).The mutant protein is subjected to high-density fermentation in a 5L fermentation tank, and the enzyme activity of the fermentation liquor can reach 4628U / mL, and the recovery rate of the mutant enzyme is increased by 1.7 times.Compared with the wild type, the optimal pH of the mutant is increased from 4.5 to 5.5, the optimal temperature is decreased from 60 DEG C to 50 DEG C, the lactose hydrolysis efficiency is increased by 11%, and the mutant is more suitable for the production process of low / zero lactose dairy products.

The present invention provides an oncolytic virus vector containing a sequence encoding IL-4 receptor targeted cargo protein, including IL-4 muteins and / or IL-13 muteins, the oncolytic virus encoded therefrom, the uses of the oncolytic virus for treating cancer.

The invention belongs to the technical field of target sample characterization, and provides application of enterococcus pore-forming toxin mutant protein in nanopore detection. The enterococcus pore-forming toxin mutant protein is EPX1 nanopore mutant protein and is obtained by mutating wild type EPX1 nanopore protein, the amino acid sequence of the wild type EPX1 nanopore protein is as shown in SEQ ID NO: 1, and the mutation means that one or more amino acids of the wild type EPX1 nanopore protein are mutated into common amino acids except original amino acids. The EPX1 protein (wild type) is a type of pore-forming toxin protein and widely exists in various living bodies in nature, and a mutant of the EPX1 protein shows excellent pore-forming capacity after being modified (after amino acid mutation). The structural stability, the molecular recognition efficiency and the detection performance of the EPX1 nanopore mutant protein are remarkably improved.

The invention provides an infectious bronchitis virus subunit vaccine as well as a preparation method and application thereof, and belongs to the technical field of genetic engineering vaccines. According to the chicken infectious bronchitis virus mutant protein disclosed by the invention, the amino acid sequence of the mutant protein is shown as SEQ ID NO.5. According to the avian infectious bronchitis virus subunit vaccine containing the recombinant avian infectious bronchitis virus mutant protein Kozak-IgKsp-IBV-M41-S-core-6His as an effective component, the glycosylation level of the vaccine is relatively high, the expression level is relatively stable, the virus return risk of a live vaccine does not exist, the safety is high, large-scale industrial preparation can be achieved, and the vaccine has good application prospects. The cost is low.

This disclosure provides compounds of Formula ( AA ) Formula ( A ), Formula ( I ) (e.g., Formula ( I-a1 )), Formula ( II ) (e.g., Formula ( II-1 ), ( II-a ), ( II-a1 ), ( II-a2 ), or ( II-a3 )), Formula ( III ) (e.g., Formula ( III-1 )), Formula ( IV ) (e.g., Formula ( IV-a ), ( IV-a1 ), ( IV-b ), ( IV-b1 ), or ( IV-c )), or Formula ( B ) (e.g., Formula ( B-1 )), or pharmaceutically acceptable salts thereof, that inhibit a KRas protein. In some embodiments, the KRas protein has a dysregulation (e.g., the KRas protein is mutated or amplified). These compounds are useful, for example, for treating a disease, disorder, or condition in which increased and / or sustained (e.g., excessive) KRas activation, for example, KRas activation associated with a mutant KRas protein, contributes to the pathology and / or symptoms and / or progression of the disease, disorder, or condition (e.g., cancer) in a subject (e.g., a human). This disclosure also provides compositions containing compounds as disclosed herein, or pharmaceutically acceptable salts thereof, and methods of using and making the same.

The present invention relates to the fields of agriculture, plant biotechnology, and molecular biology. Specifically, the present invention relates to a wheat EPSPS mutant protein and use thereof in improving the tolerance of wheat to glyphosate. The mutant protein comprises an amino acid sequence having the following mutations compared to the EPSPS amino acid sequence of any genome of wild-type wheat: in the amino acid sequence set forth in SEQ ID NO: 2, the amino acid at position 168 is mutated from threonine to isoleucine, the amino acid at position 169 is mutated from alanine to valine, and the amino acid at position 172 is mutated from proline to serine. The mutant protein enables the production of stable glyphosate-resistant wheat, showing important significance for wheat breeding.

The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R1-R5, R5A, and L are defined herein. These compounds are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.

The invention relates to a method for regulating and controlling the color of wheat grains and reducing the germination rate of the grains, a related TaMyb10 mutant protein, a gene, a gene editing vector and application of the TaMyb10 mutant protein. The invention discloses a method for regulating and controlling the color of wheat grains and reducing the germination rate of the grains. The method comprises the step of inhibiting or destroying the interaction of TaMyb10 protein and bHLH protein in wheat to obtain white-grain pre-harvest germination resistant wheat. The invention further discloses a functional segment which is combined with bHLH in the TaMyb10 protein and can influence the color and the pre-harvest germination resistance of wheat grains, application of a variant of the functional segment, TaMyb10 mutant protein containing substitution and / or deletion and / or addition of amino acid residues at one or more functional sites of the functional segment, and application of the TaMyb10 mutant protein. The interaction between the TaMyb10 and the bHLH protein is weakened or does not interact with the bHLH protein through the mutation of the amino acid at the functional site, so that the wheat shows the characteristic of white-grain pre-harvest sprouting resistance, and the cultivation of the white-grain pre-harvest sprouting resistance wheat variety is facilitated.

Disclosed are a new interleukin-2 (IL-2) mutant protein and the use thereof. Compared with wild-type IL-2, the IL-2 mutant protein has improved properties, such as an improved IL-2 receptor binding property and improved druggability. Also provided are a fusion protein, dimer and immunoconjugate comprising the IL-2 mutant protein, nucleic acids encoding the IL-2 mutant protein, the dimer and the immunoconjugate, and a vector and host cell comprising the nucleic acid. Further provided are methods for preparing the IL-2 mutant protein, the fusion protein, the dimer and the immunoconjugate, a pharmaceutical composition containing same, and the therapeutic use thereof.

The invention discloses an IL-2 mutant and a fusion protein of the IL-2 mutant and an anti-PD-1 antibody. In particular to an IL-2 mutant protein with the following mutation sites: Q11R, E15D, D20E, K35E, L36E, T37L, R38E, M39E, L40K, R81Q and / or Q126R, and a fusion protein containing the IL-2 mutant protein and a PD-1 antibody. The fusion protein provided by the invention reduces the affinity with an IL-2 receptor, can significantly inhibit the growth of tumors, and has good safety. The fusion protein PD-1 / IL2m disclosed by the invention can be effective on tumors which are ineffective in PD-1 treatment, meanwhile, through mutation of IL-2, the safety is improved while the activity of the PD-1 / IL-2 fusion protein is ensured, and the fusion protein has a wide clinical application prospect in the anti-tumor field.

The invention provides a method for improving the expression level of a meat toxin light chain. The method comprises the following steps: connecting a dissolution-promoting tag to an N end or a C end of meat toxin light chain protein to form soluble meat toxin light chain recombinant protein; the dissolution-promoting tag is a wild dissolution-promoting tag NT11 or a mutant protein mut7 of the wild dissolution-promoting tag NT11, enzyme digestion removal is not needed, the activity of a meat toxin light chain is hardly influenced and interfered, and the fusion protein can keep 93% of substrate enzyme digestion activity. The method further comprises overexpressing a molecular chaperone htpG in the genome of the host bacterium. According to the invention, a BoNT / A-LC high-efficiency expression system is constructed through multi-strategy optimization, so that the yield of BoNT / A-LC is increased by nearly 20% compared with that of wild type NT11-Lc, the yield reaches 647 mg / L through overexpression of a molecular chaperone htpG, and after combinatorial optimization, the yield is 8.5 times that of only expressed BoNT / A Lc, 1.79 times that of NT11-Lc and 1.43 times that of Mut7-Lc.

This invention discloses a method for the bioenzymatic synthesis of deoxynucleoside monophosphate. The invention provides a mutant protein of dNK, comprising mutating amino acid residues at positions 84, 88, 110, and 172 of the amino acid sequence shown in SEQ ID NO:1, while leaving other amino acid residues unchanged, to obtain a protein with deoxynucleoside kinase activity. This invention obtains a deoxynucleoside kinase mutant capable of stably and efficiently catalyzing the synthesis of 3'-O-NH2-deoxynucleoside monophosphate using 3'-O-NH2-deoxynucleoside as a substrate, providing a new approach and pathway for nucleotide production. The bioenzymatic synthesis of (deoxy)nucleoside monophosphate of this invention has advantages such as high conversion rate, mild reaction conditions, simple production process, environmental friendliness, and ease of large-scale production.

The application discloses application of SbWOX gene and SbBBM gene in corn breeding and a corn genetic transformation method, and relates to a bioengineering technology.The application provides a nucleic acid molecule with co-expression of SbWOX protein gene and SbBBM protein gene, and corresponding gene co-expression vectors and microbial transformants.The application also provides application of the co-expression of the SbWOX gene and the SbBBM gene in the corn genetic transformation method.The application obtains corresponding genes and mutant proteins based on the SbWOX gene and the SbBBM gene of sorghum, the two genes are co-expressed in the corn genetic transformation process, even without adding plant growth hormones in the antibiotic screening medium in the tissue culture process, the plant genetic transformation process can be normally completed, and the transformation efficiency and the regeneration efficiency of the corn can be remarkably improved, the transformation rate reaches 10.42%, and the differentiation rate reaches 32.89%.

The application discloses a LCC with enhanced hydrophobicity ICCG The application discloses a mutant protein and application thereof ICCG The mutant protein is obtained by mutating an amino acid residue at the 266th amino acid residue in a protein amino acid sequence into phenylalanine, and is a mutant N266F. Compared with a wild-type protein, the mutant protein has significantly enhanced hydrophobicity, and is verified by a PET depolymerization experiment. The mutant protein has significantly improved PET depolymerization efficiency compared with the wild-type protein under the condition of low enzyme load, is economically feasible, and has product selectivity.

The application discloses a five-heterocycle compound, a preparation method and application thereof. Specifically disclosed are a compound as shown in formula I, a pharmaceutically acceptable salt or solvate thereof, a composition containing the compound, and a pharmaceutical use of the compound for preparing a drug for treating a disease or disorder related to the mechanism of action of KRAS G12C mutant protein. The five-heterocycle compound in the application has the activity of inhibiting the proliferation of Ba / F3 KRAS-G12C cells, NCI-H358 cells and MIA PaCa-2 cells expressing KRAS G12C mutant protein, and has a good inhibitory effect on the growth of a subcutaneous transplanted tumor of a NCI-H358 nude mouse.

The invention discloses a lactic dehydrogenase LdLDH mutant and application thereof, a wild type LdLDH enzyme derived from Lactobacillus delbrueckii subsp. Bulgaricus is taken as a research object, the amino acid sequence of the wild type LdLDH enzyme is designed and modified to obtain a mutant protein, the mutant protein is named as LdLDH-M, the amino acid sequence of the mutant protein is shown as SEQ ID NO.2, the Tm value of the LdLDH-M is 77.1 DEG C, the Tm value of the LdLDH-M is 77.1 DEG C, and the Tm value of the LdLDH-M is 77.1 DEG C; compared with the wild type LdLDH enzyme, the Tm value of the LdLDH enzyme is increased by 27.4 DEG C, and the enzyme activity of the LdLDH enzyme is increased by 1.4 times. Therefore, compared with the wild type LdLDH enzyme, the LdLDH-M has remarkably improved thermal stability and enzymatic activity, and is more beneficial to widening the application range of the LdLDH-M in the fields of high-temperature biological research, industrial biological catalysis and the like.

The invention discloses a glycolaldehyde synthetase mutant and application of the glycolaldehyde synthetase mutant in improving the thermal stability of glycolaldehyde synthetase, and belongs to the technical field of biological catalysis application. According to the glycolaldehyde synthetase mutant disclosed by the invention, on the basis of an amino acid sequence as shown in SEQ ID NO.1, the glycolaldehyde synthetase mutant has the following mutations: A381P / E509F, A381P / K290P, A381P, S61A, A381P / K290P / E509F, A381P / C49A, A381P / T100V, A381P / S61A or A381P / K290P / S61A. The mutant protein can catalyze formaldehyde to prepare hydroxyacetaldehyde (glycolaldehyde). In addition, the mutant protein can also improve the catalytic efficiency from formaldehyde to glycolaldehyde, and due to the improvement of the thermal stability, continuous catalysis of industrial enzyme in actual reaction is facilitated, so that the mutant has a good industrial application prospect.

The invention discloses a method for synthesizing deoxynucleoside monophosphate by a biological enzyme method. The mutant protein of dNK provided by the invention is a protein with deoxynucleoside kinase activity, which is obtained by mutating amino acid residues at 84th, 88th, 110th and 172nd positions on an amino acid sequence as shown in SEQ ID NO: 1 and keeping amino acid residues at other positions unchanged. According to the present invention, the deoxynucleoside kinase mutant is obtained, 3 '-O-NH2-deoxynucleoside can be adopted as the substrate, the 3'-O-NH2-deoxynucleoside monophosphate can be stably and efficiently catalyzed and synthesized, and the new thought and the new approach are provided for nucleotide production. The (deoxy) nucleoside monophosphate synthesized by the biological enzyme method has the advantages of high conversion rate, mild reaction conditions, simple production process, environmental friendliness, easiness in large-scale production and the like.

A class of KRAS G12C mutant protein inhibitors, specifically disclosing the compound shown in formula (I), and an isomer and a pharmaceutically acceptable salt thereof.

A long-acting FGF21 derivative, specifically relating to an FGF21 derivative comprising an FGF21 mutant protein and a fatty acid chain. The FGF21 derivative, which is obtained by coupling the fatty acid chain to a cysteine residue at position 172 of an FGF21 protein by means of a linker, has relatively high FGF21 activity, and has a better weight loss effect in model mice. The FGF21 mutant protein not only retains the activity of mature FGF21, but also has significantly improved stability in serum.

A Vip3Aa mutant protein and the use thereof in controlling pests. The mutant insecticidal protein Vip3Aa contains an amino acid sequence having the following mutations compared with the amino acid sequence as shown in SEQ ID NO: 1: in the amino acid sequence corresponding to that as shown in SEQ ID NO: 1, the amino acid at position 24 is mutated from tyrosine into any other amino acid; the amino acid at position 27 is mutated from alanine into any other amino acid; the amino acid at position 36 is mutated from methionine into any other amino acid; and / or the amino acid at position 28 is mutated from phenylalanine into any other amino acid. The Vip3Aa mutant protein has a significantly improved insecticidal activity compared with a wild-type Vip3Aa, and has a good insecticidal effect on Lepidoptera insects such as Spodoptera frugiperda.

A fusion protein comprising an anti-PD1 antibody moiety having a C-terminus, and an IL21 mutant protein conjugated to the anti-PD1 antibody moiety having a C-terminus wherein the IL21 mutant protein comprises at least one of two mutations relative to wild-type IL21: (1) one of a K72Y substitution, a K72M substitution and a K72Q substitution, and (2) a 75-80 deletion. In some examples, the anti-PD1 antibody may take the ETYY format and may comprise: a first heavy chain comprising a VH comprising the sequence of SEQ ID NO: 11; and a second heavy chain comprising a VH comprising a sequence selected from the sequences of SEQ ID NO: 8-10. Also provided are pharmaceutical compositions comprising the fusion protein, nucleic acids encoding the fusion protein, vectors comprising the nucleic acids, and methods of administering the fusion protein to treat diseases.

The present application relates to the application of Klenow mutant fragments in the synthesis of nucleic acids, and belongs to the technical field of biological modification and synthesis.The present application provides the application of Klenow mutant fragments with an amino acid sequence as shown in SEQ ID NO.8 or SEQ ID NO.14 in the synthesis of nucleic acids.The mutant protein F762A expressed by the Klenow mutant fragments of the present application can efficiently synthesize deoxyribonucleic acid, ribonucleic acid, deoxyribonucleic acid analogs and ribonucleic acid analogs with different lengths of DNA templates and DNA / RNA primers at 37 DEG C, and has a wide synthesis range and universality.

This invention pertains to fusion protein mutants comprising a Prime Editing enzyme having a first amino acid sequence and a second amino acid sequence, wherein the first amino acid sequence comprises a SpCas9 H840A nickase mutant protein of SEQ ID NO:152 and the second amino acid sequence comprises a Moloney Murine Leukemia Virus reverse transcriptase protein mutant (MMLV RTase mutant), wherein the fusion protein mutant displays at least the equivalent or greater activity of a reference Prime Editing enzyme in genome editing.

The application discloses a novel trimeric recombinant protein vaccine. Specifically disclosed are a mutant protein RBD8M with an amino acid sequence of SEQ ID No. 1 and a fusion protein of positions 26-277, positions 1-277 and SEQ ID No. 4. The application also discloses a vaccine containing the fusion protein, and further develops a trimeric recombinant protein vaccine containing the fusion protein and a double adjuvant. Experiments show that the vaccine prepared in the application can effectively induce cellular immunity and humoral immunity of the body in animals, a trace amount of the protein can stimulate a very high immune response of mice, has a good protection effect, can simultaneously produce high-titer neutralizing antibodies against various epidemic strains of the novel coronavirus, is a broad-spectrum effective new coronavirus vaccine, and has important significance for preventing novel coronavirus infection and a wide clinical application prospect.