4179 results about "Protide" patented technology

The invention relates to the technical field of computer-aided drug design, in particular to a drug molecule screening and optimizing method based on artificial intelligence prediction, which comprises the following steps: S1, obtaining a dynamic protein conformation set and molecular multi-dimensional characterization: obtaining a dynamic conformation set of a target protein and a physicochemical property spatial distribution diagram of a binding pocket of the dynamic conformation set, a two-dimensional molecular map topological structure and three-dimensional conformation coordinates of the drug molecules are obtained; s2, multi-modal fusion prediction is carried out; s3, generating interpretable optimization guidance; and S4, automatic iterative optimization: performing batch prediction and screening on the new candidate molecular structure, taking the screened optimal molecule as a new starting point, repeatedly executing the interpretability optimization guidance generation step and the step until an iteration termination condition is met, and outputting a final optimized molecule list. Through the multi-modal fusion deep learning model, the interaction strength of the drug molecules and the target protein can be quickly and accurately predicted, and the screening efficiency of the drug molecules is greatly improved.

The invention discloses a drug resistance prediction method and system based on comparative learning and multi-modal fusion, and the method comprises the steps: firstly generating a molecular map and a molecular fingerprint based on the SMILES of a target drug, and extracting the molecular features of the drug through a comparative learning model constructed through combining a map attention network and a map convolution network; and then, acquiring protein expression, gene expression and metabolic expression data from the target tissue cells, extracting modal features through a deep convolutional network, a Transform encoder and a multi-dimensional attention network, and realizing adaptive fusion of the multi-modal features through a heterogeneous interactive attention mechanism. And finally, jointly inputting the fused multi-modal features and drug molecular features into a multi-layer sensor to realize high-precision prediction of the drug resistance of cells to drugs. By introducing a contrast learning and multi-modal feature fusion mechanism, the characterization capability and prediction precision of the model are effectively improved, and efficient and reliable support can be provided for drug screening and clinical decision making.

The present disclosure provides compositions and methods for prime editing with improved editing efficiency and / or reduced indel formation with modified prime editors and prime editor fusion proteins. The disclosure further provides, vectors, cells, and kits comprising the compositions and polynucleotides of the disclosure.

The invention provides an UTR (Untranslated Region) element H2202 P1-G as well as a construction method and application thereof, and relates to the technical field of mRNA (messenger ribonucleic acid). According to the present invention, the ribosome load prediction and the secondary structure optimization are performed on the natural 5 'UTR of the HIV TAT 202 gene through the BaidleHelix platform, and the obtained HTAT 202 P1 sequence avoids the inhibitory hairpin structure so as to significantly improve the luciferase expression quantity compared to the natural UTR; an ncRNA sequence without a secondary structure is introduced on the basis of the HTAT 202 P1, translation inhibition of a 5 'cap region is further relieved, and the protein expression quantity of the constructed H2202 P1-G mutant (the DNA sequence of the H2202 P1-G is as shown in SEQ NO 1, and the RNA sequence is as shown in SEQ NO 2) is further improved.

Disclosed in the present invention are a KRAS G12D degradation agent as well as a preparation method therefor and the use thereof. The present invention provides compounds as shown below, and / or stereoisomers, enantiomers, diastereoisomers, atropisomers, deuterated compounds, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof. The compounds provided by the present invention can effectively degrade and / or inhibit KRAS G12D protein in cells, and can be used for preparing drugs for treating and / or preventing related diseases or disorders caused by KRAS G12D mediation. G-L-E I

The invention discloses a colorectal cancer drug relocation method based on multi-omics integration. The system comprises a multi-omics data acquisition and preprocessing module, a tumor microenvironment analysis module, a specific disease network construction module, a multi-dimensional drug relocation module and a result evaluation module. And the tumor microenvironment analysis module comprises cell heterogeneity identification, cell map construction, cell annotation and tumor cell subset annotation. The specific disease network construction module comprises tumor feature expression program extraction, expression program screening, meta-program construction, clinical related meta-program recognition and specific disease protein interaction network construction. And the multi-dimensional drug relocation module comprises a module for identifying diseases by using a random walk algorithm, carrying out drug screening based on disturbance data, carrying out drug screening based on network proximity and carrying out comprehensive drug relocation. From the perspective of single cell data, element programs related to colorectal cancer survival are excavated, corresponding modules are designed, and the efficiency and precision of colorectal cancer targeted drug screening are improved.

The invention discloses an application of a medicago sativa MsDGK5 gene and a protein coded by the medicago sativa MsDGK5 gene in salt stress resistance of plants, and belongs to the technical field of plant genetic engineering. The nucleotide sequence of the medicago sativa MsDGK5 gene provided by the invention is as shown in SEQ ID NO. 1. According to the application, MsDGK5 gene overexpressed arabidopsis thaliana and medicago sativa transformation plants are constructed, growth and development indexes and physiological and biochemical parameters of the plants under salt stress are systematically measured, and it is proved that overexpression of the MsDGK5 gene can significantly improve the salt tolerance of the transgenic plants. Based on the experimental results, the key regulation effect of the MsDGK5 gene in plant salt tolerance is defined for the first time, an important gene resource is provided for crop salt tolerance genetic improvement, and a new technical approach is also provided for coping with the increasingly aggravated soil salinization problem.

The invention discloses a self-replicating RNA (Ribonucleic Acid) molecule, a porcine rotavirus RNA vaccine and application thereof, and relates to the technical field of vaccines. According to the present invention, the coding sequence of the porcine rotavirus G9P23 type VP4 protein is optimized, such that the fact that the saRNA prepared by using the nucleotide sequence represented by the SEQ ID NO: 10 can secrete the high porcine rotavirus G9P23 type VP4 protein antigen after the cell transfection is found; after the optimized porcine rotavirus G9P23 type VP4 protein is used for immunizing experimental animals, the level of neutralizing antibodies generated by the animals can be improved, and the challenge protection effect is enhanced. Therefore, the nucleic acid molecule provided by the invention can be used for developing drugs and vaccines for causing protective immune response in experimental animal bodies. Compared with a traditional vaccine, the vaccine provided by the invention has good immunogenicity and safety, and has a good application prospect.

This invention belongs to the field of biological detection technology, specifically relating to a monoclonal antibody combination for detecting feline NT-proBNP protein and its applications. The monoclonal antibody combination of the present invention comprises monoclonal antibodies 3A6 and 5H5. These two antibodies possess unique heavy and light chain variable region complementarity-determining regions, respectively, and their amino acid sequences have been fully defined (SEQ ID NOs. 1-12). This antibody combination can specifically recognize and efficiently bind to feline NT-proBNP protein, making it suitable for the development of a highly sensitive and specific diagnostic tool for feline cardiomyopathy. By constructing a double-antibody sandwich ELISA assay system, the minimum detection limit can reach 100 pg / mL, and it exhibits excellent specificity and stability.

The invention discloses erianin PROTACs as well as a preparation method and application thereof, the structural formula of the erianin PROTACs is # imgabs0 #, E3 Ligand is pomalidomide, and Linker is an alkane chain or a PEG chain. The erianin PROTACs disclosed by the invention are superior to the prior art in the aspects of target protein degradation efficiency, anti-tumor activity, innovativeness, application prospect and the like, and show remarkable technical progress and practical value.

The present invention discloses an interfering RNA for inhibiting PCSK9 gene and use thereof. The interfering RNA comprises a nucleotide sequence set forth in any one or two or more of SEQ ID NOs: 1-40, 73-96. The interfering RNA of the present invention can better target and silence hepatic PCSK9 mRNA, reduce the protein level of PCSK9, enhance LDL-C metabolism, and reduce serum cholesterol, providing a solid technical foundation for the development of siRNA medicaments for the prevention, treatment, and symptom alleviation of PCSK9 gene-mediated diseases.

The invention specifically discloses a composition for detecting NAD < + > and application thereof, and relates to the technical field of biological detection. According to the composition for detecting NAD < + >, the composition comprises an NAD < + > binding protein fragment A connected with an Fc tag, an NAD < + > binding protein fragment B and a connecting peptide, the detection result is accurate and reliable, and meanwhile the technical difficulty, uncertainty and high cost faced by antibody screening in a traditional method are avoided.

The invention provides a fluorescent protein selection marker staygold-ynaMr gene and application thereof, and belongs to the technical field of biological engineering. The method comprises the following steps: replacing codons of L-isoleucine in nucleotide sequences of a fluorescent protein gene staygold and a gene ynaM by using a rare codon ATA to respectively obtain the fluorescent protein gene staygold after codon replacement and the gene ynaMr after codon replacement, and connecting the two segments of genes after codon replacement by using a flexible protein peptide, and the fluorescent protein selection marker staygold-ynaMr gene is obtained. Experiments prove that the gene can obviously improve the screening efficiency of L-isoleucine high-yield strains.

Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing proteins or protein domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing proteins or domains, are provided.

The invention discloses a specific antibody MR-34 for targeting a coronavirus MERS-CoV spike protein RBD (Radial Basis Disease). The sequences of the CDRs of the antibody disclosed by the invention are as shown in SEQ ID NO. 1 to SEQ ID NO. 6. The antibody provided by the invention contains CDRs with a specific sequence, and can be specifically combined with an MERS-CoV spike protein RBD structural domain. The antibody provided by the invention is strong in targeting property and high in binding activity, and the antibody prepared by the preparation method provided by the invention is high in purity and can be prepared on a large scale. On the whole, the antibody disclosed by the invention can be used for developing and optimizing an MERS-CoV infection detection method.

The invention discloses an interfering RNA (Ribonucleic Acid) for inhibiting a PCSK9 gene and application of the interfering RNA. The interfering RNA comprises any one or more than two nucleotide sequences as shown in SEQ ID NO: 1-40 and SEQ ID NO: 73-96. The interfering RNA can better target and silence mRNA of the liver PCSK9, reduce the protein level of the PCSK9, enhance LDL-C metabolism and reduce serum cholesterol, and a solid technical basis is provided for research and development of siRNA drugs for prevention and treatment of PCSK9 gene mediated diseases and symptom relief.

The present invention relates, in part, to chimeric proteins comprising consensus interferon, or a variant thereof, and their use as therapeutic agents.

The invention discloses a micromolecule NSD3 degradation agent as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The invention provides a micromolecular NSD3 degradation agent, which has a structure as shown in a formula I or a formula II, has a remarkable inhibition effect on NSD3 protein expression, and has remarkable killing and growth inhibition effects on lung squamous carcinoma cells. The small molecule NSD3 degradation agent provides a new scheme for treatment of lung squamous cell carcinoma, and has a good clinical application prospect. # imgabs0 # imgabs1 #

The present disclosure provides compositions and methods for the targeted modification of RNA molecules by RNA prime editing. The compositions and methods may be conducted invitro or in vivo within cells (e.g., human cells) for the therapeutic correction of disease-causing mutations and / or installation of motifs or mutations in RNA molecules of interest as a tool for scientific research. The disclosure provides compositions and methods for conducting RNA prime editing of a target RNA molecule (e.g., an RNA transcript) that enables the incorporation of one or more nucleotide changes and / or targeted mutagenesis of a target RNA molecule. The nucleotide change can include a single-nucleotide change, an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides a variety of configurations of the RNA prime editors each comprising a nucleic acid programmable RNA binding proteins (napRNAbp), such as Cas13, and an RNA-dependent RNA polymerase (RDRP), which are provided as fusion proteins or which can be separately provided in trans. The RNA prime editors are guided to a target RNA site by a guide RNA, which can be a rpegRNA that includes a template region for the synthesis of an RNA sequence to be installed on the RNA molecule attached to an available 3′ terminus. In others embodiments, the RNA template can be provided in trans.

According to the GPX4 protein degradation agent and the application, the degradation agent serves as molecular glue to induce tumor cell ferroptosis and is different from an existing PROTAC technology, and the molecular glue can induce interaction between E3 ubiquitin ligase and target protein GPX4 and promote ubiquitination of the E3 ubiquitin ligase and the target protein GPX4. Compared with the existing GPX4 degradation agent, the molecular glue has the advantages of small molecular weight, high cell permeability and better druggability. The GPX4 molecular glue disclosed by the invention can be used for effectively degrading GPX4 and has a killing effect on various tumor cell lines. The preparation method is simple in synthesis route and mild in reaction condition, can be used for being developed into a new generation of GPX4 targeting drugs, and has great clinical application value and considerable market potential.

The invention relates to the technical field of plant genetic engineering, and particularly discloses an alfalfa salt-alkali-resistant and low-temperature composite stress-resistant gene MsNCED5 and application of encoded protein thereof in improving salt-alkali-resistant and low-temperature composite stress-resistant capability of plants. The nucleotide sequence of the gene disclosed by the invention is as shown in SEQ ID NO.1, the full length is 1833 bp, and 610 amino acids are encoded. According to the invention, an MsNCED5 overexpression vector is constructed and medicago sativa is converted, so that an MsNCED5-OE transgenic line is successfully created, and the MsNCED5 gene expression quantity of the MsNCED5-OE transgenic line is obviously increased compared with that of a wild type. Under the salt-alkali and low-temperature composite stress, the transgenic plant has stronger stress tolerance compared with the wild plant, which indicates that the overexpression of the MsNCED5 gene improves the resistance of the plant to the salt-alkali and low-temperature composite stress. The MsNCED5 gene disclosed by the invention provides an important theoretical basis for researching an alfalfa stress resistance molecular mechanism and breeding.

Described herein are programmable DNA proteolytic target chimera complexes that can be used both for the direct treatment of cancer by inhibiting biochemical pathways that are overexpressed in cancer cells, and for the indirect treatment of cancer by recruiting the E3 ligase complex to engage with a protein of interest or a mutant thereof and initiating proteolysis. Also described herein are methods of using the complexes in the treatment of cancer, as well as compositions comprising the complexes.

The invention provides a double-target degradation molecule based on a functionalized nucleic acid connexon and application thereof, and relates to the technical field of biological medicine, the double-target degradation molecule comprises an E3 ubiquitin ligase ligand at one end, a first target protein ligand at the other end, and the functionalized nucleic acid connexon located between the E3 ubiquitin ligase ligand and the first target protein ligand; the functionalized nucleic acid linker is a nucleotide sequence capable of specifically recognizing and combining a second target protein or a coding gene thereof, so that the protein level degradation of the first target protein and the nucleic acid level or expression level inhibition of the second target protein / gene are realized in the same molecule. Functionalized nucleic acid and a PROTAC strategy are organically combined, single-molecule double-target collaborative intervention is achieved, targeting efficiency and treatment potential are improved, higher flexibility and expandability are provided in synthesis and design, and a new molecular platform and technical route are provided for multi-target accurate treatment.

The invention discloses a small CRISPR (clustered regularly interspaced short palindromic repeats)-Cas gene editing system and application thereof. According to the invention, based on microbial genome and metagenome data, a class of CRISPR-Cas family protein is mined through a biological information method, and is named as Cas12r. A CRISPR-Cas12r editing tool constructed on the basis of the gene can realize gene editing in prokaryotic or eukaryotic cells. The CRISPR-Cas12r gene editing system obtained by the invention has the characteristics of miniaturization and various PAM types.

This invention discloses a milk protein containing composition comprising: at least one milk protein; at least a first protein; at least a second protein; and at least a linker comprising an amino acid sequence coded by nucleotide sequence which is at least 80% similar to sequences selected from the group consisting of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, and SEQ ID NO: 21

The invention discloses a shark source nano antibody targeting an FPV-VP2 protein and an application of the shark source nano antibody. The amino acid sequence of the complementarity determining region 3 of the shark source nano antibody is selected from any one of the sequences shown in SEQ ID NO.16 to SEQ ID NO.30, or a sequence having homology with the sequence shown in any one of the sequences shown in SEQ ID NO.16 to SEQ ID NO.30; the amino acid sequence of the shark source nano antibody is selected from any one of the sequences shown in SEQ ID NO.1-SEQ ID NO.15, or the amino acid sequence of the shark source nano antibody is selected from any one of the sequences shown in SEQ ID NO.1-SEQ ID NO.15, or a sequence having homology with the sequence shown in any one of the sequences shown in SEQ ID NO.1-SEQ ID NO.15. The shark source VNAR nano antibody has the advantages of small molecular weight, high affinity, high stability, easiness in genetic engineering modification, low production cost and the like.

The invention relates to the field of molecular targeted therapy, and discloses an application of an SLC16A5 (MCT6) small-molecule inhibitor MCT6-Ai7-2 in preparation of a medicine for treating acute myeloid leukemia (AML). The inhibitor takes an SLC16A5 protein structure predicted by Alphafold as a target spot, and is obtained through compound database screening, molecular docking and druggability optimization. An in-vitro experiment proves that MCT6-Ai7-2 can remarkably inhibit proliferation of AML cell lines such as U937 and MOLM-13, induce cell apoptosis and retard a cell cycle, has an inhibiting effect on a primary AML patient specimen and is relatively low in toxicity to normal cells; in-vivo experiments show that the compound is effective and has good safety in AML model mice. In addition, the MCT6-Ai7-2 and the vinca can be combined to synergistically enhance the inhibition effect on vinca drug-resistant cells, and by reducing the expression of anti-apoptotic protein MCL-1, the activation of pro-apoptotic factors BIM and tBID is promoted to play a role. The invention provides a novel targeting drug and strategy for treatment of AML (especially drug-resistant or recurrent patients).

The invention discloses three pattern recognition protein Hc beta GRP genes for preventing and treating fall webworms, dsRNA and application thereof. Specifically, the nucleotide sequences of the three pattern recognition protein Hc beta GRP genes for preventing and treating fall webworms are respectively SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3. The recombinant Hc beta GRP protein is successfully obtained through a prokaryotic expression system, an in-vitro bacteriostatic test proves that the recombinant Hc beta GRP protein, the Hc beta GRP protein and the dsRNA have direct bacteriostatic activity, dsRNA is designed based on a pattern recognition protein Hc beta GRP gene, a hyphantria cunea Hc beta GRP dsRNA interference system implemented by using an injection method is established, an obvious gene silencing effect is obtained by injecting the Hc beta GRP dsRNA interference system into hyphantria cunea, and the Hc beta GRP dsRNA interference system is applied to the hyphantria cunea. The technical support is provided for the application of the Hc beta GRP RNAi technology. Besides, the dsRNA of the hyphantria cunea Hc beta GRP is combined with the biocontrol bacteria by utilizing an established hyphantria cunea Hc beta GRP RNA interference system, so that the control effect of the biocontrol bacteria can be remarkably improved.

The invention relates to the field of biological detection, in particular to a monoclonal antibody combination for detecting human IL-6 protein and application. The combination comprises monoclonal antibodies 3A10 and 2G1, and amino acid sequences of complementary determining regions of variable regions of light and heavy chains of the monoclonal antibodies 3A10 and 2G1 are respectively shown as SEQ ID NO.1-12. The invention defines a complete variable region sequence and a coding nucleotide sequence of the antibody. The combination specifically recognizes human IL-6 recombinant and natural proteins, and has no cross reaction with IL-11. A double-antibody sandwich ELISA kit constructed based on the combination takes 3A10 as a coating antibody and 2G1 as a labeled antibody, and has high sensitivity and high specificity. The problems that an existing reagent is insufficient in specificity and low in sensitivity are solved, a reliable core raw material is provided for IL-6 standardized detection, and the method is suitable for preparation of a kit, a test strip and an antibody chip.

The invention relates to a nano antibody Nb3-18 capable of identifying and neutralizing SFTSV (swine fever with thrombocytopenia syndrome), which comprises three complementary determining regions CDR1-3, and the sequences of the three complementary determining regions CDR1-3 are respectively shown as SEQ ID NO: 1-3. Nanometer antibody drug development and diagnostic kit research and development are carried out on SFTSV which is high in fatality rate but lacks effective vaccines and specific antiviral drugs, the nanometer antibody VHH which is specifically combined with GN is screened through the platform technology of preparing GN protein, inactivating viruses, immunizing alpaca, displaying nanometer monoclonal antibodies through a phage library and the like, the CDR sequence of the nanometer antibody VHH is identified, and the SFTSV with the high fatality rate is obtained. A humanized antibody Nb3-18 is constructed; meanwhile, the curative effect of Nb3-18 in treating SFTSV infection is evaluated at the in-vitro cell level. The invention provides a potential nano antibody new drug for clinical treatment of SFTSV, and also provides a corresponding detection kit for diagnosis of SFTSV.