394 results about "Target binding" patented technology

The present disclosure features methods, compositions, and kits for determining the location of a target nucleic acid and / or detecting the presence or absence of a genetic variant in a biological sample using an array with capture probes comprising a spatial barcode and one probe which has complementarity to the capture probe, binds to target and is extended. A second probe which binds to the extended first probe and is extended and bound to capture probe. Location and genetic variant are determined by sequencing of the extended probe.

The invention provides a drug target binding affinity prediction method based on multi-modal data fusion. The method comprises the following steps: firstly, extracting sequence feature information of drug SMILES and target FASTA, then constructing an affinity graph, modeling drug molecules and target protein molecules into an undirected graph, and extracting molecular-level features of atoms, bonds, residues and contact. And fusing the hierarchical graph structure information of the affinity graph and the molecular graph to obtain the graph structure feature representation of the drug-target spot. The sequence feature information and the graph structure feature representation are further fused by using intramolecular and intermolecular attention fusion mechanisms. And finally, performing affinity prediction by using the fused features, and outputting a drug-target binding affinity score. According to the method, sequence and structural information are effectively fused, the accuracy of drug target affinity prediction is improved, and the problems of insufficient information fusion and insufficient structural information utilization in an existing method are solved.

The invention relates to a humanized nano antibody targeting cadherin 17 and application of the humanized nano antibody, and relates to the technical field of immunology and molecular biology. The complementarity determining region of the humanized nano antibody comprises a CDR1 of which the amino acid sequence is shown as SEQ ID NO: 2, a CDR2 of which the amino acid sequence is shown as SEQ ID NO: 4 and a CDR3 of which the amino acid sequence is shown as SEQ ID NO: 6; a framework region of the humanized nano antibody comprises an FR1 of which the amino acid sequence is shown as any one of SEQ ID NO: 1 and SEQ ID NO: 8, an FR2 of which the amino acid sequence is shown as any one of SEQ ID NO: 3, SEQ ID NO: 9 and SEQ ID NO: 11, an FR3 of which the amino acid sequence is shown as any one of SEQ ID NO: 5 and SEQ ID NO: 10, and an FR4 of which the amino acid sequence is shown as SEQ ID NO: 7. According to the humanized nano-antibody, the immunogenicity of the nano-antibody is reduced, the targeted binding activity and killing activity are improved, and the humanized nano-antibody can be used for developing immunodetection reagents, CAR-T / NK cell drugs and antibody drugs.

The present disclosure provides in some embodiments, a multi -objective binder design framework by aligning autoregressive molecular foundation models (e.g., protein language models (pLMs)) to different objectives, such as binding and developability considerations. In some embodiments, direct preference optimization (DPO) can be utilized in the methods and systems described herein to encode multiple design objectives in the language model through direct optimization on expert curated preference sequence datasets comprising preferred and dispreferred distributions. In some embodiments, utilizing the described framework can enable molecular foundation models (e.g., protein language models), such as ProtGPT2, to effectively design binders conditioned on specified receptors and one or more drug developability criteria. Besides being multi -objective, in some embodiments, the methods and systems provided herein conceive online lab-in-the-loop design pipelines by actively incorporating experimental feedback.

The invention relates to the technical field of radiopharmaceuticals, and in particular relates to a bicyclo [1.1. 1] pentane compound for targeting and combining fibrocyte activating protein and application of the bicyclo [1.1. 1] pentane compound. The structure of the compound as shown in the formula (I) is # imgabs0 # (I); according to the invention, the structure of the FAP combined compound is modified, so that the compound with longer residence time in in-vivo tumors is obtained.

The invention relates to a Nectin-4 binding peptide and an application thereof. The amino acid sequence of the Nectin-4 binding peptide comprises an amino acid sequence as shown in any one of SEQ ID NO. 1 to SEQ ID NO. 19, and an amino acid sequence as shown in any one of SEQ ID NO. Or the amino acid sequence is obtained by substitution, insertion and / or deletion of at least one or more amino acids compared with the amino acid sequence as shown in any one of SEQ ID NO.1-SEQ ID NO.19. The target binding peptide is developed aiming at the extracellular region of the Nectin-4, and the obtained Nectin-4 binding peptide has high affinity with the Nectin-4, can recognize the Nectin-4, can be specifically bound with the Nectin-4, can be used as a drug for treating individual tumors or cancers, provides a new strategy for treating Nectin-4 related diseases, and opens up a new way for treating cancers and other related diseases.

The invention relates to the technical field of radiopharmaceuticals, in particular to a targeted binding fibrocyte-activated protein polymer compound and application thereof. The structure of the compound as shown in the formula (I) is # imgabs0 # (I); according to the invention, the structure of the FAP combined compound is modified, so that the compound with longer residence time in in-vivo tumors is obtained.

A query-based generic end-to-end molecular optimization (“QMO”) system framework, method and computer program product for optimizing molecules, such as for accelerating drug discovery. The QMO framework decouples representation learning and guided search and applies to any plug-in encoder-decoder with continuous latent representations. QMO framework directly incorporates evaluations based on chemical modeling, analysis packages, and pre-trained machine-learned prediction models for efficient molecule optimization using a query-based guided search method based on zeroth order optimization. The QMO features efficient guided search with molecular property evaluations and constraints obtained using the predictive models and chemical modeling and analysis packages. QMO tasks include optimizing drug-likeness and penalized log P scores with similarity constraints and improving the target binding affinity of existing drugs to pathogens such as the SARS-CoV-2 main protease protein while preserving the desired drug properties. QMO tasks further improves optimizing antimicrobial peptides toward lower toxicity.

The invention discloses a drug molecule generation optimization method based on deep reinforcement learning, in order to overcome the problems of unbalanced distribution of existing drug and target point data and the like, a backbone network structure of an LSTM and transformer structure is established to solve the generation optimization of drug molecules, a local module is improved to reinforce performance, then reinforcement learning is added, and the drug molecule generation optimization method based on deep reinforcement learning is realized. The attributes of molecules generated in each round are processed to serve as loss of deep learning and award of reinforcement learning, and the model is dynamically corrected, so that high-quality drugs which can be effectively combined with target spots, are high in water solubility and moderate in stability and can be easily absorbed by human bodies can be designed. The measurement standard adopted by the attribute optimization task is chemical conversion property MMPs, and the hydrophobicity, solubility and clearance rate of molecules are used as evaluation indexes. By adopting the model provided by the invention, on the basis of ensuring the basic stability of a new drug, better target binding activity can be obtained.

The present application relates to a composition comprising (a) at least one immune checkpoint inhibitor and (b) at least one conjugate, wherein said conjugate is comprising (i) a target binding moiety, (ii) at least one amatoxin, and (iii) optionally at least one linker connecting said target binding moiety with said at least one amatoxin. The present application further relates to said composition for use in treating a patient having a cancer, and to a pharmaceutical formulation comprising said composition and additional excipients, as well as to methods of producing and using said composition (FIG. 1).

The invention discloses a BimBH3 analogue containing D-type amino acid and N-terminal fatty acid acylation, a preparation method of the BimBH3 analogue and application of the BimBH3 analogue as a PTPN1 inhibitor to development of hypoglycemic drugs. The structural general formula of the novel BimBH3 mimic peptide analogue is shown as a formula I: # imgabs0 #, wherein Raa2 is equal to D-His, D-Leu, D-Pro, D-Ser, D-Arg, D-Gln, D-Lys, D-Trp, D-Val, D-Tyr, D-Ala, Raa3 is equal to D-Gln, Raa7 is equal to D-Arg, and Raa8 is equal to D-Allo-Ile. The mimic peptide compound is derived from a core region of a Bim-BH3 structural domain, different D-type amino acid site-specific replacement modification and N-terminal conjugated hexadecanoic acid modification are adopted for amino acids at the second, third, seventh and eighth sites respectively, the BimBH3 mimic peptide modified by the D-type amino acid is more stable and has higher metabolic stability, and the target binding capacity and inhibitory activity of the BimBH3 mimic peptide can still be reserved or even improved. The BimBH3 mimic peptide compound shows an excellent PTPN1 inhibitor, the ability of resisting protease hydrolase and various digestive enzymes is also remarkably improved, and the BimBH3 mimic peptide compound has longer pharmacological action time and can play a potential long-acting hypoglycemic role through subcutaneous injection or oral administration. The compound is completely prepared by a polypeptide solid-phase synthesis method, and an obtained crude product is subjected to semi-preparative liquid chromatography purification and freeze-drying to obtain a target compound.

The present application relates to a compound or a pharmaceutically acceptable salt and / or solvate thereof comprising one or more circulation enhancing groups, one or more target binding groups, one or more chelating groups, at one least cleavable linker and at least one branching group that is at least trivalent. The application further includes a radionuclide complex or a pharmaceutically acceptable salt and / or solvate thereof, comprising a compound of the application or a pharmaceutically acceptable salt and / or solvate thereof, and one or more radionuclides, and to compositions comprising the compound or the complexes. The present application also includes methods of using the compounds, complexes and compositions for targeting and / or killing target cells. For example, the compound includes a compound of Formula I

The invention discloses a leukemia targeted therapy preparation as well as a preparation method and application thereof. Comprising a DNA nanoflower carrier targeting leukemia cells through a PTK7 receptor and benzene arsenic oxide loaded on the carrier. The DNA nanoflower carrier is obtained by rolling circle amplification, and a nucleic acid aptamer complementary sequence of targeted binding leukemia cells is introduced into a template chain subjected to rolling circle amplification. The preparation method comprises the following steps: modifying sulfydryl onto a DNA nanoflower by using DNA-Dithiol, then breaking a disulfide bond by using reduced glutathione to expose the sulfydryl, and loading benzene arsenic oxide onto the DNA nanoflower through a reaction between trivalent arsenic and the sulfydryl. The structure of the DNA nanoflower has a high surface area and high porosity, and can load a large amount of PAO, so that the killing performance on cancer cells is enhanced; the aptamer sgc8 sequence is introduced into the DNA nanoflower, so that the targeting of the DNA nanoflower to cancer cells is effectively realized; the preparation also has the advantages of being good in thermodynamic stability, easy to store, excellent in biocompatibility and the like, and has a very good application prospect.

The invention discloses a lipopolysaccharide response type nano antibacterial peptide as well as a preparation method and application thereof, and belongs to the technical field of biology, and the amino acid sequence of the antibacterial peptide is as shown in SEQ ID No.1. Meanwhile, the invention further discloses application of the antibacterial peptide in preparation of drugs for treating gram-negative bacterium infectious diseases. The antibacterial peptide disclosed by the invention can be combined with lipopolysaccharide in a targeted manner to form nanofibers for capturing, and then the nanofibers are clustered and presented to phagocytes for phagocytosis, so that killing of beneficial bacteria in a host is fully avoided. In conclusion, the antibacterial peptide disclosed by the invention can target gram-negative bacteria to rupture membranes and sterilize, fully avoid mistakenly killing beneficial bacteria in a host body and effectively reduce the generation of drug resistance, so that the antibacterial peptide is a nano capture peptide with an immune regulation function, which has great development potential and relatively high application value.

The invention relates to the technical field of biological medicine, in particular to a polypeptide self-assembly PROTAC degradation agent and a preparation method and application thereof. The polypeptide self-assembly PROTAC degradation agent comprises a self-assembly group, an E3 ligase recognition group, a cathepsin response group, an FOXM1 targeting binding group, a connecting peptide and an integrin alpha 6 targeting peptide, the amino acid sequence of the FOXM1 targeted binding group is as shown in SEQ ID NO: 1. According to the polypeptide-based nano delivery system, the drug delivery efficiency is remarkably improved, meanwhile, the risk of side effects is reduced to the minimum through controllable release of active fragments, and a basis is provided for preparation of tumor drugs.

The present application relates to conjugates comprising an amatoxin, a target-binding moiety wherein the target is CD37, i.e., a CD37-binding moiety, and optionally a linker linking said amatoxin and said CD37-binding moiety. The invention further relates to the synthesis of said conjugates. In addition, the invention relates to a pharmaceutical composition comprising such conjugate for use in the treatment of immune cell, particularly B-cell and / or lymphoma associated diseases and / or malignancies (FIG. 1).

The invention discloses a compound-target binding affinity prediction method based on multi-modal feature fusion, and relates to the technical field of compound activity prediction, and the technical key point is that the method comprises the steps of data acquisition, multi-modal feature characterization, multi-modal feature extraction and fusion, and affinity prediction to predict the compound activity. The problems of long time consumption, high cost, low efficiency and the like of compound activity prediction are solved through assistance of an artificial intelligence algorithm, and information can be processed in parallel in a self-adaptive and self-learning manner by referring to a multi-layered structure of a human brain and a layer-by-layer analysis processing mechanism of neuron information interaction. The intensity information of the interaction between the compound-target pair is provided by combining the affinity, the affinity between the compound and the target is predicted through a deep learning method, and the specific biological activity and key action target of the compound are analyzed.

Provided herein a compound and compositions that bind to p62 and a target of interest, and promote degradation of the target of interest. In some embodiments, a compound described herein is a compound of formula I: A-B-C (I) or a pharmaceutically acceptable salt thereof, wherein A is an agent that binds or associated with p62; B is a linker moiety; and C is a target binding moiety.

The invention discloses a resource binding method, electronic equipment and a storage medium. The method comprises the steps that in response to an interrupt request to be processed of a target instance, a target binding strategy is determined, and the target binding strategy is used for determining that a network card interface corresponding to the interrupt request and processor resources to be bound with the interrupt request are located in the same resource node of a processor architecture; and carrying out resource binding processing on the interrupt request according to the target binding strategy to obtain a binding processing result. The technical problem of poor network performance caused by sequential binding of processor resources only according to the interrupt number in the prior art is solved.

The embodiment of the invention discloses a chip testing method and device, a management service platform and electronic equipment, and the method comprises the steps that the management service platform enables a first target binding result to be matched with first preset binding information, and sends second preset binding information to a testing machine when the matching succeeds, and setting each test board card on the test machine based on second preset binding information to obtain a second target binding result, and when the second target binding result is successfully matched with the second preset binding information, testing each target tested device by the test machine to obtain a test result. Therefore, the first target binding result corresponding to each test board card on the loading and unloading machine table is matched with the first preset binding information, and the second target binding result on the test machine table is matched with the second preset binding information, so that the target tested device is prevented from being arranged on an unusable slot position; and it is ensured that the test board card can be accurately arranged in a corresponding test machine.

The invention relates to application of anti-PTPRZ1 chimeric antigen receptor macrophages in lung cancer treatment, and belongs to the technical field of tumor targeted therapy. The invention constructs a novel chimeric antigen receptor (CAR) which comprises a coding sequence of a single-chain variable region fragment for specifically recognizing PTPRZ1, and a coding sequence of a CD8TM transmembrane region and a coding sequence of a CD3zeta intracellular signal transduction structural domain. The design ingeniously endows the chimeric antigen receptor (CAR) with high specificity, so that the chimeric antigen receptor (CAR) can accurately recognize and firmly bind to the surface of a tumor cell expressing PTPRZ1 protein. According to the present invention, the chimeric antigen receptor targeting PTPRZ1 is successfully transfected into the human macrophage to form the CAR-M. A flow cytometry verifies that compared with non-transfected macrophages (Mphi) or transfected macrophages lacking a specific target binding domain (CAR-M-delta), the CAR-M has the advantage that the efficiency of swallowing PTPRZ1 positive tumor cells is remarkably improved in the aspect of the efficiency of swallowing PTPRZ1 positive tumor cells. Therefore, the CAR-M constructed by the invention can be used as a potential treatment means for targeting PTPRZ1 expression tumors.

The invention relates to the technical field of genetic engineering antibodies, in particular to a bispecific antibody combined with BCMA and CD3 as well as a preparation method and application of the bispecific antibody. The invention provides a bispecific antibody which can be combined with BCMA and CD3 at the same time, has a specific targeting effect and can efficiently excite oriented immune response. The bispecific antibody well retains the biological functions of an anti-CD3 antibody and an anti-BCMA antibody, realizes that one bispecific antibody molecule simultaneously has an excellent BCMA and CD3 targeted binding biological function, can build a bridge between tumor cells and immune effector cells, effectively activates the immune effector cells and oriented immune response, and has a good application prospect. The tumor cell killing effect of immune cells is remarkably enhanced, the target cell killing efficiency is high, the ADCC effect is reduced to the maximum degree, high safety is achieved, and good application prospects are achieved in tumor immunotherapy.

The method, the composition and the kit provided by the invention provide a signal amplification method for detecting target biomolecules, and the sensitivity of detecting by using target binding ligand molecules is remarkably improved. These methods include adding nucleic acid repeat cycles to, for example, a target binding molecule, thereby providing a plurality of landing pads for the labeled probe. These methods are well suited for multiplex detection, so that multiple targets can be sensitively detected in one detection. The methods and compositions can be applied to the fields of imaging, flow cytometry, mass spectrometers / CyTOF and the like, and provide additional tools for research and diagnosis purposes.

The invention relates to the technical field of bioinformatics and artificial intelligence, and provides a drug-target interaction prediction method and system based on multi-modal feature fusion, and the method comprises the steps: carrying out the word segmentation coding of an obtained to-be-recognized drug sequence and a target sequence, and respectively extracting the subsequence features of a drug and a target; constructing a two-dimensional molecular diagram of the drug and a three-dimensional structure diagram of the target, and respectively extracting diagram structure characteristics of the drug and the target; fusing the subsequence features and graph structure features of the drug and the target through a cross attention mechanism; and carrying out interactive fusion by adopting a bidirectional collaborative attention mechanism to obtain a prediction result of the binding affinity of the drug and the target. According to the invention, by combining the multi-modal complementary information of the drug and the target, deep interaction between different modal features is deeply mined; meanwhile, a two-way collaborative attention mechanism is introduced into interaction modeling of the drug and the target, and the accuracy of drug-target binding affinity prediction is effectively improved.

Provided for herein are viral particles comprising a heterologous viral glycoprotein and a targeting moiety, wherein the targeting moiety comprises a polypeptide comprising a formula of T-S1, wherein T is a target binding domain and S1 is a stalk portion. As provided for herein, the viral particles further comprises a nucleic acid molecule encoding for a heterologous molecule of interest. As provided for herein, the heterologous molecule of interest may be a tandem CAR. Also provided for herein are compositions comprising the same, and methods of using the same.

Provided herein are multi-chain chimeric polypeptides that include:(a) a first chimeric polypeptide including a first target-binding domain, a soluble tissue factor domain, and a first domain of a pair of affinity domains; and (b) a second chimeric polypeptide including a second domain of a pair of affinity domains and a second target-binding domain, where the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains. Also provided here are methods of using these multi-chain chimeric polypeptides and nucleic acids encoding these multi-chain chimeric polypeptides.

The invention relates to the technical field of biology, in particular to a chimeric antigen receptor of a specific targeting tumor non-classical HLA molecule, polynucleotide, an expression vector, a recombinant virus, a recombinant cell, a composition and pharmaceutical application. An extracellular domain of the chimeric antigen receptor specifically combined with the HLA-G in a targeted manner is an antigen binding structural domain of an ILT2 receptor, and compared with a CAR modified immune cell with an antigen binding region of an antibody as an extracellular domain, the HLA-G targeted immune response cell provided by the invention can recognize numerous tumor cells in a broad-spectrum manner on one hand, so that the HLA-G targeted immune response cell can be used for preparing an HLA-G targeted immune response cell; the killing efficiency and accuracy of various tumor cells are greatly improved; and on the other hand, the extracellular domain is an antigen binding domain of an ILT2 receptor, and the binding domain is a binding domain of a natural receptor, so that compared with an artificially synthesized antibody, the antigen binding domain is safe and reliable, and can truly reflect the target binding capacity in a natural state.

The invention discloses a fusion protein taking peptide-N-glycosidase as an active component as well as a preparation method and application of the fusion protein, and belongs to the technical field of biological medicines. The fusion protein comprises: (a) peptide-N-glycosidase or a catalytically active fragment thereof; (b) an immunoglobulin Fc domain, or a combination of a tumor or immune cell antigen binding domain and an immunoglobulin Fc domain; (c) a linker peptide; wherein the form of the tumor or immune cell antigen binding domain is Fab, scFv or VHH; the peptide-N-glycosidase or the catalytic activity fragment of the peptide-N-glycosidase is connected with the Fc structural domain of the immunoglobulin through the connecting peptide; the immunoglobulin Fc domain mediates the fusion protein to form a homodimer or a heterodimer. According to the invention, the synergistic function of targeted binding and local deglycosylation of the target molecule is realized, so that the immunosuppressive activity of the target molecule is interfered, and the anti-tumor immune response is enhanced.

The invention relates to an HDAC11 binding polypeptide and application thereof. The amino acid sequence of the HDAC11 binding polypeptide comprises an amino acid sequence as shown in any one of SEQ ID NO. 1 to SEQ ID NO. 20, and an amino acid sequence as shown in any one of SEQ ID NO. Or the amino acid sequence is obtained by substitution, insertion and / or deletion of at least one or more amino acids compared with the amino acid sequence as shown in any one of SEQ ID NO.1-SEQ ID NO.20. A targeted binding peptide is developed aiming at an HDAC11 extracellular region, and the obtained HDAC11 binding polypeptide has high affinity with HDAC11, can recognize and bind HDAC11, can be used as a drug for treating individual tumors or cancers, provides a new strategy for treating HDAC11 related diseases, and opens up a new way for treating cancers and other related diseases.

The present disclosure provides a polypeptide complex comprising a target binding polypeptide that binds to a molecule on a target cell or a molecule in an extracellular matrix (ECM); and small latent complexes comprising in particular a dimer latent related polypeptide (LAP) or a fragment or derivative thereof, and a dimer mature transforming growth factor beta (TGF beta) family polypeptide or a fragment or derivative thereof. Polypeptides (e.g., fusion polypeptides), and related polynucleotides, vectors, cells, and pharmaceutical compositions are also provided. Also provided are methods of treating subjects using, for example, these polypeptide complexes and / or these fusion polypeptides or pharmaceutical compositions thereof.