317 results about "Protein targeting" patented technology

The invention provides a fibroblast activating protein targeting compound, a nuclide marker of the fibroblast activating protein targeting compound, a pharmaceutical composition containing the fibroblast activating protein targeting compound and application of the fibroblast activating protein targeting compound and the nuclide marker, and relates to the technical field of nuclide drugs. The fibroblast activating protein targeting compound comprises a compound shown as a formula I, and has remarkably enhanced tumor uptake and retention time. The invention also relates to a pharmaceutical composition and a kit containing the targeting compound, and application of the compound in diagnosis or treatment of fibroblast activating protein overexpression diseases. # imgabs0 #

The present disclosure relates to a novel class of bifunctional molecules that are useful in a targeted or selective degradation of a protein.

Provided are compounds that may bind a target protein, and result in modification of the target protein. The compounds may further bind a modifier protein. The modifier protein may carry out or enhance the modification of the target protein. The modification may activate or reactivate the target protein. Also provided are methods of using the compounds.

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 discloses application of an AI-driven target screening technology in anti-obesity treatment of a drug delivery system, and belongs to the field of cross fusion of biological medicine and artificial intelligence. The screening method provided by the invention comprises the following steps: selecting a signal channel target and active small molecules related to lipid metabolism; processing the signal channel target and the active small molecules through the data set to obtain an input matrix; and inputting the input matrix into a deep learning model to obtain the interaction intensity between the active small molecules and the signal path target. According to the method, an artificial intelligence technology is introduced, a deep learning model is constructed to efficiently predict the affinity between a drug and a protein target, the problems that a traditional target screening method depends on experience and is low in efficiency are solved, and target expression is subjected to experimental verification through a molecular biology method, so that the target screening efficiency is improved. A verification closed loop from calculation prediction to molecular demonstration is realized, and the biological credibility of a target screening result is proved.

The invention discloses methanogen lyase homologous with a PeiR lyase sequence and application of the methanogen lyase, and aims to solve the problem that PeiR lyase protein of a methanogen cell wall peptide bond can participate in a biological process of hydrolyzing archaea cell walls, effectively kill methanogen and reduce methane production, and protein homologous with the PeiR lyase protein has potential methane reduction potential. According to the invention, a series of biological information software is utilized to identify protein sequences coded by methanogens virus from rumen microbiome sequencing data, and sequence homology between the proteins and PeiR protein is further analyzed to obtain a series of methanogens lyases. In order to realize the expression of the lyase, multiple segments of primers are designed to synthesize a target sequence, and the target sequence is successfully expressed in a prokaryotic expression system. Through the detection of crude enzyme liquid, the effectiveness of the lyase in the aspect of reducing the methane yield is verified in an in-vitro gas production test.

Disclosed in the present invention is a novel substituted heterocyclic compound having VAV1 target degradation activity. Specifically disclosed is a compound serving as a VAV1 target degradation agent and having the structure of formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, isotopic substituent or isomer of the compound. The compound can be used for preventing or treating diseases related to VAV1 targets or signaling pathways.

The invention discloses methanogen lyase homologous with high-dimensional characteristics of PeiW lyase and application of the methanogen lyase, and aims to solve the problem that PeiW lyase protein of methanogen cell wall peptide bonds can participate in the biological process of hydrolyzing archaea cell walls, effectively kill methanogen and reduce methane production, and protein homologous with the protein has potential methane reduction potential. According to the method, a series of bioinformatics software is utilized, a protein sequence coded by methanogens virus is identified from a large amount of rumen microorganism virus group sequencing data, the high-dimensional homology of a deep learning model between the protein sequence and PeiW is analyzed, and two methanogens lyases similar to the high-dimensional characteristics obtained by the PeiW model are obtained. In order to realize the expression of the lyase, multiple segments of primers are designed to synthesize a target sequence, and the target sequence is successfully expressed in a prokaryotic expression system. Through detection of a crude enzyme solution, the effectiveness of the lyase in the aspect of reducing the yield of methane is verified in an in-vitro gas production test.

The invention discloses an oligonucleotide intracellular nano delivery system based on polypeptide modification and application thereof. The system is composed of a periostin targeting sequence (SDSSD), a matrix metalloproteinase 2 (MMP2) response sequence (GPAGLLG), a cell penetrating sequence (RRRRRRRR, R9), a reactive oxygen species (ROS) scavenging and adhesion enhancing group (Gly-DOPA)) and a terminal dibenzocyclooctyne (DBCO) modified engineered polypeptide SDSSD-PEG5-YGFGG-GPAGLLG-R9-(G-DOPA) 3-K4-C-DBCO, and a target oligonucleotide miRNA-26a-A5-Azido modified by 5-polyadenylic acid (AAAAA) and an azide group (Azido), and the target oligonucleotide miRNA-26a-A5-Azido, the target oligonucleotide and assembling through a click chemical reaction and a non-covalent interaction. The nano system has good bone targeting, enzyme responsiveness, intracellular delivery effect and biological safety, can realize stable and efficient delivery of therapeutic oligonucleotides in vivo, and significantly improves the utilization efficiency and therapeutic potential of oligonucleotides. The oligonucleotide intracellular nano delivery system has a wide application prospect in the fields of clinical transformation and precise treatment of oligonucleotide drugs.

The invention relates to application of a vitamin E compound in preparation of a MACIR protein targeting agent. The vitamin E compound comprises any one or a combination of at least two of tocopherol, tocopherol derivatives, tocotrienol or tocotrienol derivatives. The invention creatively discovers the interaction between tocopherol, tocopherol derivatives, tocotrienol or tocotrienol derivatives and MACIR protein, and proves the strong binding capacity of tocopherol or derivatives thereof and MACIR protein through experiments. The tocopherol, the tocopherol derivative, the tocotrienol or the tocotrienol derivative can be used for regulating the function of MACIR protein associated immune cells so as to influence the expression of inflammatory factors, play an important role in inflammation and anaphylaxis, and also can be used for improving skin injury repair.

The present invention relates to a fibroblast activation protein alpha (FAP)-targeting conjugate comprising Formula I: Y-L-X, wherein Y is a chelator or cytotoxic drug, L is a linker, and X is a molecule comprising a cyclic peptide of formula A-[Z-AA1-AA2-AA3-AA4-AA5-AA6-AA7-Z]-B. A is N-terminal structure. B is C-terminal structure, and each of the Z, AA1, AA2, AA3, AA4, AA5, AA6, AA7 is a residue of an amino acid.

The invention discloses a nano degradation agent for targeted degradation of PI3Kalpha protein as well as a preparation method and application of the nano degradation agent. The nano degradation agent comprises a polyamidoamine dendritic polymer G3-NH2, a PI3Kalpha protein targeted receptor and an HSC70 protein targeted receptor, wherein the PI3Kalpha protein targeted receptor and the HSC70 protein targeted receptor are coupled to the surface of the polyamidoamine dendritic polymer G3-NH2. The prepared nano degradation agent enters cells in an endocytosis mode, specifically targets corresponding treatment targets after entering the cells, and then efficiently degrades PI3Kalpha protein through a molecular chaperone-mediated autophagy pathway of lysosome, so that the PI3Kalpha protein can be effectively degraded. The nano degradation agent provided by the invention can be applied to intervention of related diseases caused by PI3Kalpha protein abnormality.

The invention provides a drug target binding affinity prediction method and system based on a multi-level connection diagram, and relates to the technical field of computational biology, the method comprises the following steps: preprocessing drug small molecules, protein targets and affinity diagrams to obtain the multi-level connection diagram, and performing node feature extraction; obtaining drug isomorphic connection diagram embedding, drug internal connection diagram embedding, protein isomorphic connection diagram embedding, protein internal connection diagram embedding and heterogeneous connection diagram embedding; fusing the heterogeneous connection diagram embedding with the drug internal connection diagram embedding and the protein internal connection diagram embedding respectively to obtain drug internal connection diagram node features and protein internal connection diagram node features; and performing feature fusion based on an attention mechanism on the drug internal connection diagram node features, the protein internal connection diagram node features, drug isomorphic connection diagram embedding and protein isomorphic connection diagram embedding to obtain a drug-protein interaction feature input classifier, and outputting a prediction result of the drug target binding affinity.

The present disclosure relates to a novel class of bifunctional molecules that are useful in a targeted or selective degradation of a protein.

The present invention relates to a fibroblast activation protein alpha (FAP)-targeting conjugate comprising Formula I: Y-L-X, wherein Y is a chelator or cytotoxic drug, L is a linker, and X is a molecule comprising a cyclic peptide of formula A-[Z-AA1-AA2-AA3-AA4-AA5-AA6-AA7-Z]-B A is N-terminal structure. B is C-terminal structure, and each of the Z, AA1, AA2, AA3, AA4, AA5, AA6, AA7 is a residue of an amino acid.

The invention discloses an LbCas12a protein mutant as well as a preparation method and application thereof, the LbCas12a protein mutant is obtained by performing K390A or K945A mutation on a wild type LbCas12a protein, and the amino acid sequence of the wild type LbCas12a protein is as shown in SEQ ID NO. 1. According to the present invention, the LbCas12a protein is subjected to directional modification, the alanine mutation occurs at the K390 / K945 site, the LbCas12a-K390A protein mutant and the LbCas12a-K945A protein mutant are prepared, the protein mutants obtained based on the method provide a series of significant advantages in function, and the solid foundation is laid for the application of the protein mutants in multiple fields. Through Michaelis-Menten kinetic analysis, it is observed that when the LbCas12a-K390A / K945A protein mutant prepared through the method and the wild type LbCas12a protein target the same dsDNA target, the catalytic efficiency of the LbCas12a-K390A / K945A protein mutant is 42.1 times that of the wild type LbCas12a, and the catalytic efficiency of the LbCas12a-K390A / K945A protein mutant is 707.9 times that of the wild type LbCas12a, and the catalytic efficiency of the LbCas12a-K390A / K945A protein mutant is 707.9 times that of the wild type LbCas12a. The results show that K390 and K945 are mutated into alanine, so that the affinity of the LbCas12a protein to a substrate can be increased to a certain extent, and the LbCas12a protein has higher trans-cleavage activity.

The invention belongs to the technical field of medicines, and particularly relates to a PARP-1 protein targeted degradation chimera compound as well as a preparation method and application thereof. The PARP-1 protein targeted degradation chimera compound is as shown in a formula (I), wherein P represents a ligand of PARP protein, Z represents a ligand of E3 ligase, and L represents a middle connecting chain part; the compound can be used for treating or preventing tumors. The PARP-1 protein targeted degradation chimera disclosed by the invention has a relatively good inhibition effect on proliferation of tumor cells, has a very high degradation effect on PARP-1 protein, and has concentration gradient dependence. (I).

The invention provides an affinity prediction method based on local interaction of a pharmacophore and a target spot, and relates to the technical field of DTA prediction, and the method comprises the steps: constructing a molecular graph and a pharmacophore graph of a drug according to the structure of the drug, coding the pharmacophore graph through a graph neural network, and obtaining an embedded vector of the pharmacophore graph; updating messages among atoms by adopting a directional message passing neural network to obtain updated embedding characteristics of the medicines; processing the updated embedding characteristics of the medicine by adopting a multi-layer gating message passing neural network to obtain medicine substructure embedding characteristics; constructing a protein map, and processing the protein map by adopting a substructure perception map neural network to obtain protein substructure embedding features; a variational auto-encoder is adopted to simulate local interaction between drug molecules and a protein target, and a predicted value of affinity is obtained. By considering the spatial arrangement and pharmacophore information of the drug molecules, efficient and accurate prediction of the affinity of the drug and the target can be realized.

Virtual screening methods are disclosed for predicting interacting compounds, from a chemical library, for proteins. The methods using an Extremely Randomized Trees (Extra Trees) machine learning model in which parent node(s) represent a decision in relation to a target-compound complex, based on a plurality of features corresponding to a protein target of the complex and a plurality of features corresponding to a compound of the complex, and leaf nodes classify the target-compound complex as either interacting or non- interacting. The Extra Trees model outputs a probability that target-compound complex is interacting, based on aggregated classifications from each decision tree. Applying the Extra Trees model to a further protein target and compounds produces a probability that each compound will form an interacting complex with the further protein target. The compounds are then ranked based on the respective probabilities, and highest probability compounds are then explored using a docking model.

The subject matter described herein is directed to antibody-CIDE conjugates (Ab-CIDEs), to pharmaceutical compositions containing them, and to their use in treating diseases and conditions where targeted protein degradation is beneficial.

The invention belongs to the technical field of medical chemistry, and particularly relates to a targeted protein degradation compound containing an SYVN1 binding compound and application of the targeted protein degradation compound. According to the invention, a series of compounds interacting with SYVN1 are found, and the compounds can be used as'warheads' to participate in ERAD and effectively degrade transmembrane protein targets. Based on the SYVN1 binding compound, a new TPD technology for hijacking ERAD is established, and a brand new platform is provided for processing TMSPs and other proteins which are difficult to target by the current TPD technology. A SYVN1 interaction compound is further connected with a known ligand interacting with a protein target through a chemical linker, a series of ERADEC molecules are generated, the molecules can significantly degrade target protein, and a new possibility is provided for targeted degradation of drugs.

The invention relates to the technical field of bioinformatics, and discloses an iterative feedback type protein targeting molecule intelligent generation method and device, and the method comprises the steps: obtaining molecular structure data, training based on the molecular structure data to obtain a molecular fragment language model, and the molecular fragment language model is used for predicting subsequent molecular fragments according to an input molecular fragment sequence; obtaining an attribute preference data set, and performing alignment fine tuning on the pre-trained molecular fragment language model based on the attribute preference data set to obtain an attribute preference alignment model; and obtaining target structure information of the target protein, taking the attribute preference alignment model as a strategy network, iteratively generating and evaluating candidate molecules through a tree search algorithm under the constraint of the target structure information until a termination condition is met, and outputting the optimized protein targeting molecules. According to the application, excellent pharmacological properties can be taken into account while the protein targeting molecule binding effect is ensured, and the molecule generation quality can be dynamically optimized.

Provided herein are cerebron degrading agent antibody conjugates (cDACs) comprising a cerebron degrading agent moiety covalently linked to an antibody. The cDACs target proteins for intracellular degradation and can be used to treat diseases and conditions.

The application provides a drug virtual screening method and device based on deep learning, wherein the method comprises the following steps: inputting all candidate compound small molecules in a candidate molecule database into a pre-trained molecular encoder respectively to obtain molecular vectorization representation of the candidate compound small molecules; constructing an index structure corresponding to the candidate compound small molecules based on the molecular vectorization representation of the candidate compound small molecules; inputting a protein target to be matched into a pre-trained protein target encoder to obtain protein target vectorization representation corresponding to the protein target; and matching the protein target vectorization representation based on the index structure to obtain a target compound small molecule corresponding to the protein target. The method establishes a full-amount mapping function of the target and the molecule through a vector calculation mode, realizes high-throughput virtual screening in a second-level calculation time, realizes rapid virtual screening of a full-amount candidate molecule library, improves the precision of the virtual screening, and increases the possibility of drug discovery.

An antigen binding protein targeting CXCR3 and the use thereof. The antigen binding protein can specifically bind to CXCR3. The antigen binding protein contains a heavy chain variable region, and the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3.

The embodiment of the invention provides a drug optimization method and system based on the overall effect of a protein network. The method comprises the following steps: constructing a protein interaction network related to a target disease, and dividing each protein target into a risk protein set and a protection protein set; respectively calculating first binding affinity data of the candidate drugs and each protein target in the risk protein set, and generating a first network comprehensive score based on the first binding affinity data; respectively calculating second binding affinity data of the candidate drugs and each protein target in the protection protein set, and generating a second network comprehensive score based on the second binding affinity data; calculating network confrontation scores of the candidate drugs according to the first network comprehensive score and the second network comprehensive score; and determining whether the candidate drug is a preferred drug based on the network adversarial score. The method can overcome the defect that a single-target drug is insufficient in curative effect due to a network compensation effect, so that safer and more effective candidate drugs are screened out.

The invention discloses a bifunctional molecule compound for inducing SHP2 protein degradation based on a DCAF16 ligand as well as a preparation method and application of the bifunctional molecule compound, belongs to the technical field of medicines, and relates to a bifunctional molecule for inducing SHP2 protein degradation based on the DCAF16 ligand as shown in a general formula (I) or pharmaceutically acceptable salt of the bifunctional molecule, and a pharmaceutical composition containing an SHP2 protein targeted degradation agent. The invention also relates to a preparation method of the compound and application of the compound in preparation of medicines for treating SHP2-mediated tumors and / or other diseases.

The application relates to the field of medicinal chemistry and provides a use of a diphenylacetonitrile compound and a protein-targeting hydrolytic chimeric compound. The application finds that a diphenylacetonitrile compound shown in formula (I) directly interacts with FEM1B, thereby serving as an inhibitor of a human E3 ubiquitin ligase substrate recognition receptor FEM1B. The application also provides a compound shown in formula (II), and the compound shown in formula (II) is a protein-targeting hydrolytic chimeric (PROTAC) drug, wherein Q2 is a target protein ligand molecule, Q1 is a FEM1B inhibitor, Q2 is combined with a target protein, thereby inducing E3 ligase FEM1B combined with Q1 to approach the target protein, leading to ubiquitination and degradation of the target protein. Experimental results show that the PROTAC drug shown in formula (II) provided by the application can specifically degrade a target protein in cells. Formula (I); formula (II).

Provided here are IRE1 degrader compounds comprising a protein target moiety covalently attached by a linker to an E3 ubiquitin ligase-binding moiety. Also provided are intermediate compositions for the preparation of IRE 1 degrader compounds and methods of treating diseases and disorders such as cancer with the IRE1 degrader compounds.

A compound including formula (I) or formula (II) for use in promoting targeted protein degradation.