484 results about "Mutated protein" patented technology

The invention relates to compounds of Formula I, II II-1, III, or III-1 and pharmaceutically acceptable salts thereof, and methods of making and using the same. The compounds of the invention are effective in inhibiting and / or degrading KRAS protein with a G12D mutation and are suitable for use in methods of treating cancers mediated, in whole or in part, by KRAS G12D mutation.

The present invention relates to a KRASG12D inhibitor and the use thereof. Specifically, provided in the present invention is a compound as shown in formula (I), and the definition of each substituent in the formula is as described in the description. In addition, the present invention further relates to a composition containing the inhibitor and the use thereof. The compound of the present invention has good tumor growth inhibitory activity, and has good safety.

Provided is an antibody-drug conjugate for use in the treatment of cancer in which one or more KRAS mutants, particularly a KRAS G12V mutant, a KRAS G12D mutant, and a KRAS G12C mutant, are expressed. Also provided are a drug and a drug-linker conjugate for use in the antibody-drug conjugate.　The present inventors have produced an antibody-drug conjugate with which a heterocyclic compound represented by formula (II) and having an activity of inducing the decomposition of KRAS mutant proteins can be delivered to cancer in which EGFRs are expressed, the production being achieved by linking the compound to an anti-EGFR antibody. The present inventors have also discovered a drug-linker conjugate for use in the antibody-drug conjugate or a salt thereof. In cancer in which EGFRs are expressed, the antibody-drug conjugate induces the decomposition of one or more KRAS mutants, particularly a KRAS G12V mutant protein, a KRAS G12D mutant protein, and a KRAS G12C mutant protein, thereby inhibiting the KRAS mutants and exhibiting an anti-tumor effect.

Disclosed in the present invention are a quinazoline compound, and a pharmaceutical composition thereof and the use thereof. Provided in the present invention is a compound as represented by formula I, a stereoisomer thereof or a pharmaceutically acceptable salt thereof. The compounds of the present invention have a good degradation effect on the KRAS protein with a G12D mutation, have a good inhibitory activity against the proliferation of tumor cells with a KRAS G12D mutation, and exhibit good pharmacokinetic properties.

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 disclosure is in the field of plant genetic engineering. Specifically, the invention relates to application of a mutant GmLn protein and an encoding gene thereof in regulation and control of soybean yield, in particular to but not limited to a method for obtaining soybeans capable of being densely planted, a method for detecting the soybeans capable of being densely planted, related primers and kits, and further relates to soybean plants capable of being densely planted and a method for improving soybean planting density. According to the method provided by the invention, the soybean target sequence is subjected to gene editing by expressing the gene editing tool in the soybean, so that the soybean which is improved in yield and can be densely planted is obtained.

The invention belongs to the field of biological catalysis, and discloses a high-activity PET hydrolase mutant and application thereof. The mutant of the thermophilic PET hydrolase provided by the invention is as shown in 1), 2) or 3): 1) a protein corresponding to an amino acid sequence SEQ ID NO.4; 2) a protein corresponding to the amino acid sequence of SEQ ID NO.6; and 3) a protein corresponding to the amino acid sequence of SEQ ID NO.8. Experiments prove that the modified mutant shows higher catalytic efficiency on PET hydrolysis and can keep activity for a long time at the optimal temperature for PET depolymerization. The activity of the mutant protein BhrM3 for catalyzing PET hydrolysis is improved by 1.82 times compared with that of a wild type and is 1.22 times that of efficient PET hydrolase LCC-ICCG, and the protein melting temperature reaches 92.9 DEG C.

The invention discloses an ochratoxin A degrading enzyme mutant and application thereof. The invention provides mutant protein of amidase MiADH, which is any one of the following changes: the amino acid sequence of the amidase MiADH as shown in SEQ ID NO: 1 is subjected to any one of the following changes: a 66th amino acid residue Y is mutated into K, or a 143rd amino acid residue H is mutated into A, or a 194th amino acid residue V is mutated into A, or a 195th amino acid residue L is mutated into A, or a 230th amino acid residue H is mutated into A, or the amino acid sequence of the amidase MiADH is mutated into A, or the amino acid sequence of the amidase MiADH is mutated into K, or the amino acid sequence of the amidase MiADH is mutated into A; or the 324th amino acid residue V is mutated into A, and the protein has the same function; experiments prove that the amide hydrolase MiADH mutant can efficiently degrade OTA, and OTA detoxification can be achieved under the high-temperature condition.

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 invention discloses a dsPETase01 plastic degrading enzyme mutant and application thereof, and relates to the technical field of bioengineering, the amino acid sequence of a wild type plastic degrading enzyme (dsPETase01) is designed and modified, 8 dsPETase01 single mutation sites or 19 combined mutation sites are provided, the thermal stability of the obtained dsPETase01 mutant is improved by about 4-21 DEG C compared with that of the wild type dsPETase01, and the dsPETase01 mutant can be used for preparing a plastic degrading enzyme. And the activity is improved by nearly 1.2-3 times. The invention also provides four preferable mutant proteins which have higher yield, activity and thermal stability compared with wild dsPETase01, have wider application conditions, are more suitable for degrading PET (Polyethylene Terephthalate) plastics, and are beneficial to large-scale production and industrial application.

The invention discloses a glucose dehydrogenase GOX-2015 mutant and application thereof, and relates to the technical field of bioengineering, the amino acid sequence of wild type glucose dehydrogenase GOX-2015 is designed and modified, that is, 18 single mutation sites and 16 combined mutation sites are provided, and the glucose dehydrogenase GOX-2015 mutant is obtained. Compared with the wild type GOX-2015, the thermal stability of the obtained GOX-2015 mutant is improved by about 2 to 13 DEG C, and the activity of the obtained GOX-2015 mutant is improved by about 1.2 to 4.5 times. The invention further provides a preferable mutant protein which has higher yield, activity and thermal stability compared with wild type GOX-2015, has wider application conditions, is more suitable for efficient production of NADPH coenzyme by a biological conversion method, and is beneficial to large-scale production and industrial application.

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 invention belongs to the technical field of biology, and discloses a bioactive peptide which is a micromolecular anti-tumor bioactive peptide derived from sea cucumber, and the amino acid sequence of the bioactive peptide is FNPDTFD. Sephadex G-15 gel chromatography and mass spectrometry technologies are used for separating, purifying and structurally identifying the sea cucumber flower enzymolysis peptide, so that the small molecule peptide with a potential anti-tumor effect is obtained. A cell viability experiment verifies that the small molecule peptide can selectively inhibit the proliferation of EGFR mutant non-small cell lung cancer cells. Besides, molecular docking and protein immunoblotting results show that the peptide can be combined with EGFR mutant protein, and the activation of a downstream Akt / mTOR signal channel is inhibited by targeting the EGFR mutant protein, so that the biological activity of resisting the non-small cell lung cancer is exerted. The bioactive peptide not only has the potential of being developed into a new generation of EGFR targeting antitumor drugs, but also has wide application prospects in the field of functional health food. The preparation process is simple, and is suitable for industrial production and market popularization and application.

The invention discloses a monocotyledon anti-glufosinate-ammonium herbicide gene, a protein, a method and application, the nucleotide sequence of the monocotyledon anti-glufosinate-ammonium herbicide gene is shown as SEQ ID NO.1, the mutation site of the gene is single base substitution, and the position of the mutation site is LOCOs04g56170 gene; the amino acid sequence coded by the nucleotide sequence SEQ ID NO. 1 is as shown in SEQ ID NO. 2. A new rice germplasm resistant to glufosinate-ammonium herbicide is obtained through experiments, by spraying glufosinate-ammonium, it is confirmed that rice containing the mutant protein has glufosinate-ammonium resistance after glufosinate-ammonium is applied, and the conservative property of the mutant protein is verified in a hybridization mode.

The invention discloses a preparation method and application of a colloidal gold immunochromatography test strip for detecting IDH1 mutant protein, and belongs to the field of rapid immunodetection. The colloidal gold chromatography test strip comprises a bottom plate, a sample pad, a nitrocellulose membrane, a water absorption pad and colloidal gold, the nitrocellulose membrane is sequentially provided with a detection line T and a quality control line C in the flowing direction of a sample, the detection line T is coated with IDH1 mutant protein, and the quality control line C is coated with a second antibody corresponding to a monoclonal antibody of the IDH1 mutant protein. Clinical tumor tissue samples collected in real time in glioma resection surgery are treated, an object to be detected and an immune gold label are mixed, incubated and dropped in a test strip sample adding hole, and the object to be detected runs along the test strip under the driving of a buffer solution and generates visual color change. The test strip has the advantages of being rapid in reaction, easy and convenient to operate, convenient to carry, high in specificity and the like, makes up the blank of an IDH1 mutant protein concentration quantitative method, and has good clinical application value.

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.

A dual function protein is disclosed. The dual function protein may be prepared by linking a biologically active protein and an FGF mutant protein to an Fc region of an immunoglobulin. The dual function protein has improved pharmacological efficacy, in vivo duration and protein stability. The dual function protein exhibits improved pharmacological efficacy, in vivo duration and protein stability. A pharmaceutical composition containing the dual function protein as an active ingredient may be effectively used as a therapeutic agent for diabetes, obesity, dyslipidemia, metabolic syndrome, non-alcoholic fatty liver diseases, non-alcoholic steatohepatitis or cardiovascular diseases.

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 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 discloses an N-acetyl glucosamine 2-epimerase mutant as well as preparation and application of the N-acetyl glucosamine 2-epimerase mutant. The mutant enzyme comprises an amino acid sequence as shown in SEQ ID No.3. The preparation method comprises the following steps: by taking a recombinant vector containing a Sumo enhancing element and a wild type N-acetyl glucosamine 2-epimerase gene as a template, carrying out PCR (Polymerase Chain Reaction) by adopting a mutation primer to obtain a mutant gene segment; transforming the mutant gene segment into an engineering bacterium to obtain a recombinant bacterium for expressing the N-acetyl glucosamine 2-epimerase mutant protein; culturing recombinant bacteria, collecting and crushing thalli, centrifuging thallus crushing liquid, and taking supernatant, so as to obtain crude enzyme liquid containing the enzyme mutant; the thermal stability of the wild-type enzyme is improved through point mutation of specific amino acid sites, and the substrate affinity and the catalytic efficiency of the mutant are superior to those of the wild-type enzyme. The mutant can be used for efficient catalytic preparation of lactulose, and has the advantages of few byproducts, high product yield and the like.

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 invention discloses a nitrilase mutant and an application of the nitrilase mutant in synthesis of chiral cyanamide. Compared with an amino acid sequence of wild nitrilase amine, the nitrilase mutant protein has the advantages that the nitrilase mutant protein has a higher amino acid sequence; mutation exists at any one or more of the following amino acid sites corresponding to the amino acid sequence as shown in SEQ ID NO.1: the 54th site, the 118th site, the 120th site, the 139th site, the 148th site, the 168th site, the 170th site, the 194th site, the 197th site, the 198th site, the 202 site and / or the 225th site. The mutant constructed by the method disclosed by the invention can be used for efficiently catalyzing a 3-substituted-glutaronitrile compound to generate an (S)-3-substituted-4-cyanobutyramide compound. According to the invention, the problem of insufficient catalytic activity of the existing enzyme is solved, and an efficient scheme is provided for green synthesis of chiral cyanamide.

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.