299 results about "Target binding" patented technology

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 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.

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 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.

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 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 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 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.

Provided herein are viral particles comprising a heterologous viral glycoprotein and a targeting moiety wherein the targeting moiety comprises a polypeptide comprising the formula T-S1 wherein T is a target binding domain and Si is a stem moiety. The stem portion may comprise a variant Fc domain. The stem portion may comprise a flexible polypeptide domain. The targeting moiety comprising the formula T-S1 may be incorporated into viral particles to help target such particles to specific cell types. Also provided herein are compositions comprising the viral particles, and methods of use thereof.

The invention relates to chemically modified oligonucleotides for use in site-directed A-to-I editing of a target RNA inside a cell with endogenous adenosine deaminase acting on RNA (ADAR), the oligonucleotide comprising a sequence capable of binding to a target sequence in a target RNA and a central base triplet (CBT) of (3) nucleotides (N-1 N0 N+1), wherein N0 is the central nucleotide directly opposite to a target adenosine in the target RNA that is to be edited, wherein the oligonucleotide comprises at least one internucleoside linkage that is a methanesulfonyl (mesyl) linkage.

The present disclosure provides a large combinatorial library of cell-permeable bicyclic peptides. The bicyclic peptides described herein include the first ring consisted of randomized peptide sequences for potential binding to a target of interest while the second ring featured a family of different cell-penetrating motifs, for both cell penetration and target binding. The library was screened against the IκB kinase α / β (IKKα / β)-binding domain of NF-κB essential modulator (NEMO), resulting in the discovery of several cell-permeable bicyclic peptides which inhibited the NEMO-IKKβ interaction, thereby selectively inhibiting canonical NF-κB signaling in mammalian cells and the proliferation of cisplatin-resistant ovarian cancer cells.

The present technology relates to in vitro diagnostic methods, kits, membrane proteins and test devices for detecting the presence and / or absence of a target in a biological sample wherein the target binds to at least one epitope of an isolated membrane protein, or at least a fragment of the isolated membrane protein comprising at least one epitope of the isolated membrane protein bound to the target.

Embodiments of the present disclosure relate to modeling DEL data using factorized molecular representations (e.g., hierarchical single and double synthon building blocks), which leverages the hierarchical structure inherent to these molecules. Using factorized molecular representations, machine learning models are trained to learn the underlying binding affinity of compounds to targets and one or more covariates (e.g., loading / repeat noise). This results in machine learning models producing improved predictions in the form of higher enrichment scores that have good correlation with compound-target binding affinity.

The present invention relates to humanized antibodies or target-binding fragments or derivatives thereof retaining target binding capacities, which bind to human iRhom2 (FIG. 1).

The disclosure relates generally to electrodes with a target-binding molecule conjugated on its surface that is overlaid with a polymer of sufficient thickness to restrict ion mobility so that the electrical double layer is moved closer to the site of target binding to the immobilized target-binding molecule. Generally, thickness of the polymer coating layer is such that a target-binding site of the immobilized target-binding molecule is not in the coating layer, e.g., the target-binding site is exposed. The disclosure also provides sensors comprising the electrode and uses of the electrodes and sensors in target analyte detection, e.g., in label-free detection of targets. WO

The invention discloses a 5-bromoindole-2-carboxylic acid methyl ester derivative as well as a preparation method and application thereof in a protein inhibitor, and relates to the technical field of synthesis and preparation of inhibitors. According to the 5-bromoindole-2-carboxylic acid methyl ester derivative, compared with a contrast product, the synthetic route steps of the prepared 5-bromoindole-2-carboxylic acid methyl ester derivative are simpler and more convenient, structural modification and preparation are easier, the application range of a substrate is widened, the yield of the product is increased, and the yield of the product is increased. The differentiated requirements on the molecular structure novelty in the field of kinase inhibitors can be met. An epidermal growth factor receptor (EGFR) inhibitor prepared from the 5-bromoindole-2-carboxylic acid methyl ester derivative is higher in inhibition efficiency on biological activity, the physiological solubility is improved more remarkably, a more excellent and stable target binding result can be shown, and the EGFR inhibitor can be used for preparing an epidermal growth factor receptor (EGFR) inhibitor. The application effect of the compound in scenes such as antitumor drug development and the like is favorably improved.

This invention discloses a KK-LC-1 targeting binding protein and its derivatives, a kit, and applications. The protein sequence of the KK-LC-1 targeting binding protein is shown in one of SEQ ID No. 2, SEQ ID No. 3, SEQ ID No. 4, and SEQ ID No. 5. The KK-LC-1 targeting binding protein of this invention has a molecular weight of only about 17 kDa, approximately one-tenth that of an antibody, exhibiting good tissue penetration. Furthermore, its production process is simple and yields high quantities. The targeting binding protein of this invention demonstrates good targeting activity against KK-LC-1-positive tumors both in vivo and in vitro, and can be used for targeted tumor drug delivery, representing a potential drug for tumor immunotherapy. Simultaneously, a KK-LC-1 serum detection kit was developed using the targeting binding protein, enabling quantitative detection of KK-LC-1 levels in the human body.

The present invention relates to monospecific or bispecific antibody molecules that specifically bind antigens of Death Receptors, which are members of the tumor necrosis factor (TNF) receptor Superfamily (TNFR-SF) with an intracellular death domain. The invention relates in particular to antibody molecules of the IgG1 isotype having a mutation in the Fc region that enhances clustering of IgG molecules after target binding. The invention further relates to a combination of antibody molecules binding different epitopes on one or more specific Death Receptors. The invention also relates to pharmaceutical compositions containing these molecules and the treatment of cancer using these compositions.

The present disclosure provides recruitment of a ULK initiation complex (e.g., a ULK1 initiation complex) used to induce selective autophagy, a process by which the degradative mechanism is targeted to specific substrates. Chimeric compounds for binding to the ULK initiation complex, comprising a ULK complex binding moiety, a linker, and a target binding moiety, are provided, as well as a target of interest.

The application discloses use of LncRNA00_178, miR-466b-3p and Gucy1b1 as acute lung injury markers or drug targets, and belongs to the technical field of biomarkers and drug targets. LncRNA00_178 can be used as a biomarker for screening or diagnosing acute lung injury, a miR-466b-3p down-regulator can be used to prepare a pharmaceutical composition for preventing and treating acute lung injury, and Gucy1b1 can be used as a drug target to prepare a drug for preventing and / or treating acute lung injury. The application has the beneficial effects that the application proposes that LncRNA00_178 and miR-466b-3p, and miR-466b-3p and Gucy1b1 have a target binding relationship. LncRNA00_178 can be used as a biomarker for screening or diagnosing acute lung injury, the silence of miR-466b-3p inhibits LPS-induced apoptosis of alveolar epithelial cells, and Gucy1b1 can be used as a drug target to prepare a drug for preventing and / or treating acute lung injury. The data provide new insights for the treatment mechanism of ALI and the identification of specific targets, and provide a new idea for the research and development of new drugs for acute lung injury, and have a wide application prospect.

The present disclosure addresses the problem of providing technology for phagocytizing unwanted cells or the like in vivo.　This protein includes, from the N-terminus to the C-terminus, (A) a target binding region that binds to a target, and (C) an SHBG-like domain of ProS.