549 results about "Mutant protein" patented technology

Provided herein are compounds of Formula (I) or tautomers, atropisomers, stereoisomers, or pharmaceutically acceptable salts thereof. These compounds are useful as KRAS mutant degraders and / or inhibitors.

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.

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 invention belongs to the technical field of bioengineering. Provided are an IscB mutein and the use thereof. Compared to the wild-type IscB protein, the IscB mutein comprises arginine at at least one of the following amino acid positions: position 84, position 96, position 102, position 111, position 159, position 368 and position 386; preferably, the IscB mutein further comprises arginine at position 401 and position 456. The relatively strong interaction between the IscB mutein and a double-stranded DNA target improves the editing activity for mammalian cell lines, which can greatly enhance the application potential of the IscB mutein as a new-generation underlying tool for gene editing, and promote the use of the IscB mutein in the aspects of precision medicine, animal model construction and crop breeding.

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 present invention belongs to the field of nucleic acid editing, and particularly the technical field of clustered regularly interspaced short palindromic repeats (CRISPRs). Specifically, provided in the present invention is a Cas mutant protein having an improved activity and an improved editing efficiency. Compared with a wild-type parental Cas protein, the Cas mutant protein of the present invention has significantly improved activity, and has a wide application prospect.

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 invention discloses mutant protein of dihydroxyacetone phosphate phosphatase and application of the mutant protein. The invention provides a phosphodihydroxyacetone phosphatase mutant protein, which is characterized in that residues of phosphodihydroxyacetone phosphatase corresponding to 21st, 36th, 42nd, 49th, 64th, 82nd, 150th and 244th sites of an amino acid sequence shown in a sequence 1 are mutated to obtain a protein with phosphodihydroxyacetone phosphatase activity; and the synthesis capability of the 1, 3-dihydroxyacetone is improved. The invention also provides related biological materials and derivatives of the protein, and application of the protein in preparation of 1, 3-dihydroxyacetone. The yield of 1, 3-dihydroxy acetone of the protein is greatly increased, compared with starting wild type dihydroxy acetone phosphate phosphatase, the yield of 1, 3-dihydroxy acetone obtained through shake flask fermentation of the dihydroxy acetone phosphate phosphatase mutant SF6-11 is increased by 1.65 times, and the yield of 1, 3-dihydroxy acetone is increased to 4.54 + / -0.09 g / L from 2.75 + / -0.07 g / L.

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 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 invention discloses efficient expression of an aspergillus oryzae beta-galactosidase mutant and application of the aspergillus oryzae beta-galactosidase mutant in dairy products. The invention belongs to the technical field of enzyme engineering and the technical field of dairy product processing, and particularly relates to efficient expression of an aspergillus oryzae beta-galactosidase mutant and application of the aspergillus oryzae beta-galactosidase mutant in dairy products. The mutant protein disclosed by the invention can be as follows: A1) a protein with an amino acid sequence of SEQ ID No.2; a2) a fusion protein which is obtained by connecting a label to the N end and / or the C end of A1) and has the same function. The mutant protein is subjected to high-density fermentation in a 5L fermentation tank, the enzyme activity of fermentation liquor can reach 4628U / mL, and the recovery rate of mutant enzyme is increased by 1.7 times. Compared with a wild type, the mutant has the advantages that the optimum pH is increased from 4.5 to 5.5, the optimum temperature is reduced from 60 DEG C to 50 DEG C, the lactose hydrolysis efficiency is improved by 11%, and the mutant is more suitable for a production process of low / zero lactose dairy products.

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.

Provided herein are methods of treating a KRAS mutant cancer (e.g., a KRAS G12C mutant cancer or a KRAS G12D mutant cancer) in a subject, comprising administering to the subject an effective amount of an agent that blocks the interaction between CD47 and SIRPα and an effective amount of a KRAS inhibitor (e.g., a KRAS G12C inhibitor wherein the cancer is a KRAS G12C mutant cancer, or a KRAS G12D inhibitor wherein the cancer is a KRAS G12D mutant cancer). Also provided are methods of stimulating phagocytosis of a population of cancer cells that express a KRAS mutant protein (e.g., a KRAS G12C mutant protein or a KRAS G12D mutant protein) by macrophages, comprising contacting the population with an effective amount of a therapeutic agent that blocks the interaction between CD47 and SIRPα and an effective amount of a KRAS inhibitor (e.g., a KRAS G12C inhibitor wherein the KRAS mutant protein is a KRAS G12C mutant protein, or a KRAS G12D inhibitor wherein the KRAS mutant protein is a KRAS G12D mutant protein).

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 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.

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.

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 invention discloses a reductive aminase mutant and application of the reductive aminase mutant in synthesis of chiral alkylated benzyl propylamine. The invention relates to a mutant protein of carbonyl reductase, which is characterized in that the mutant protein has one or more alternative mutations in sites 85, 87, 128, 134, 162, 197, 219, 234 and 235 on the basis of an amino acid sequence as shown in SEQ ID NO: 1. On the basis of analysis of the crystal structure of reductive aminase M5 in the early stage, stereoselective transformation is carried out through site-specific mutagenesis, combinatorial mutation and the like, an efficient mutant for synthesizing an alkylated benzyl propylamine S-enantiomer is obtained, and a series of chiral amines with the selectivity larger than 99% S are synthesized with different amine donors such as benzyl acetone and benzylamine as substrates. And the method has important significance on industrial green synthesis of the chiral amine.

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.