63 results about "High affinity binding" patented technology

The invention discloses a bipeptide modified bionic nano-vesicle as well as a preparation method and application thereof, and belongs to the field of biological medicines. The dipeptide modified bionic nano-vesicle comprises nano-particles formed by PLGA (poly (lactic-co-glycolic acid)), and the nano-particles are loaded with a medicine with a nerve protection or nerve repair effect; the surface of the nanoparticle is coated with a macrophage membrane for expressing RVG peptide and T7 peptide. The bipeptide modified bionic nano-vesicle simultaneously presents T7 peptide and RVG peptide through an engineered macrophage membrane, the T7 peptide is combined with a blood-brain barrier transferrin receptor through high affinity to realize efficient brain entry, astrocytes in the brain are specifically recognized by virtue of the RVG peptide, accurate recognition and delivery of target cells in a focus area are realized, and the bipeptide modified bionic nano-vesicle has a good application prospect. Meanwhile, the natural inflammation tropism and immune escape ability of a macrophage membrane are reserved, and the problems that a traditional drug delivery system is low in targeting precision, and cross-barrier distribution and intracerebral distribution are difficult to cooperate are solved.

The invention relates to the technical field of organic detection, in particular to a nanoparticle modified quantum dot MOF material and a preparation method and application thereof. A zirconium-based double-ligand metal organic framework material is used as a carrier, a co-reaction accelerant Ti3C2 quantum dot is modified to enhance the electrochemical luminescence reaction efficiency, and copper-gold nanoparticles are loaded to amplify signals. The nanoparticle modified quantum dot MOF material provided by the invention can be prepared into an aptamer biosensor for accurately identifying malathion, and has high sensitivity and high selectivity. According to the invention, a nanoparticle modified quantum dot MOF material is coupled and combined with an aptamer, and an aptamer probe with high electrochemical luminescence activity and specific sensitivity to malathion is constructed. When the malathion acts on the aptamer probe, the malathion is combined with the aptamer in a high affinity manner, the aptamer probe is separated from the surface of the electrode, and meanwhile, an electrochemical luminescence signal is changed, so that the malathion residue in the agricultural product is rapidly detected.

The invention discloses a preparation method and application of a cat main allergen FEL-1 nano antibody FEL-1-Nb, and relates to the technical field of antibody preparation, and the preparation method comprises the following steps: preparing an immunogen; animal immunization and library construction; constructing and panning a phage display library; screening and identifying positive clone; and expression and purification of the nano antibody: cloning the positively cloned VHH gene to an expression vector such as a pET series, transforming an expression strain such as escherichia coli BL21 (DE3), carrying out IPTG induced expression, and purifying through an inclusion body purification method to obtain a high-purity nano antibody protein. The nano antibody FEL-1-Nb provided by the invention can be specifically bound with a cat main allergen FEL-1 protein, the unique amino acid sequence of the nano antibody FEL-1-Nb is shown as SEQIDNO: 1, high-affinity binding with the FEL-1 protein is ensured, the positive clone binding rate is high through phage display panning and ELISA verification, the phage recovery rate after the third round of panning is increased by more than 1000 times compared with the first round of panning, and the positive clone binding rate is higher than that of the first round of panning. Therefore, the nano antibody has excellent targeted recognition capability.

The application discloses a kind of nanobody specifically targeting human and murine NKG2D protein and its preparation method and application.The nanobody or antigen-binding fragment thereof of the application has three complementarity determining regions CDR1, CDR2 and CDR3;Wherein the amino acid sequences of CDR1, CDR2, CDR3 are as shown in SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4 respectively.The nanobody can simultaneously bind hNKG2D and mNKG2D with high affinity, and the bispecific nanobody E5 / 2-B12 based on the nanobody can specifically bind CEACAM5 positive tumor cells and NKG2D overexpression cells, and effectively activate NK cells, which can significantly inhibit tumor growth and prolong survival in various tumor models, and has good application prospect in tumor immunotherapy.

The application discloses application of a pyrimidinotriazine diketone derivative in preparation of a medicine for inhibiting activity of human protease caspase-1, and belongs to the technical field of medicines. In view of defects of existing caspase-1 inhibitors, the compound has the characteristics of high affinity binding to caspase-1 (K D = 8.11 μM; 8.78 μM) and strong inhibition on the activity (IC 50 = 11.90 nM-14.47 nM). The compound is used for preparation of a medicine for inhibiting the activity of caspase-1 and a medicine for treating inflammation-related diseases such as sepsis-related lung injury, acute respiratory distress syndrome or acute pancreatitis.

The invention relates to the technical field of organelle separation, and provides a method for rapid purification of peroxisome and oxidation regulation analysis of ultra-long chain fatty acid. The method comprises the following steps: introducing a nucleic acid sequence for coding a fusion protein into a target cell to obtain a cell material, the fusion protein comprising a truncated sequence derived from a peroxisome membrane protein and a tag sequence for affinity purification; taking the cell material as a sample, and separating the peroxisome with the fusion protein from the cell by utilizing an affinity ligand on the basis of a high affinity binding principle. Therefore, according to the method disclosed by the invention, the peroxisome can be rapidly and efficiently enriched, and the whole purification process can be completed within 30 minutes, so that the experimental period is greatly shortened; core protein components of target organelles can be efficiently reserved, and the metabolic activity of peroxisome can be maintained through a complete membrane structure and an internal environment; meanwhile, the same purified sample can synchronously support proteome and metabolome analysis, and direct association of'protein-metabolism 'data is realized.

The invention discloses a method for preparing a VA-ECMO lung injury treatment medicine by using ginkgolide A to regulate YARS1, and relates to the technical field of biological medicine, the method comprises the following steps: by using ginkgolide A as a YARS1 protein regulator, preparing the medicine for treating the VA-ECMO lung injury through virtual screening, binding affinity confirmation and cell efficacy confirmation; wherein the virtual screening is based on a protein structure model of YARS1, and bilobalide A with high affinity binding energy with YARS1 is screened out through molecular docking. It is proved that ginkgolide A can effectively improve the lung ventilation function by regulating YARS1, repair the alveolar epithelial barrier structure and inhibit the inflammatory oxidative stress reaction, and the lung injury treatment effect and clinical transformation safety under the support of VA-ECMO are improved.

The application relates to the technical field of biopharmaceuticals, and discloses a PD-1 and CTLA-4 double-target inhibiting polypeptide or a pharmaceutically acceptable salt thereof and an application thereof, wherein the polypeptide has a structure as shown in formula (I): X1SPILYQMCDYKRX2 (I). The polypeptide or the pharmaceutically acceptable salt thereof can simultaneously produce high-affinity binding to PD-1 and CTLA-4, has excellent biological blocking activity, can significantly improve the proportion of effector T cell subgroups in tumor tissues, and effectively enhances the anti-tumor immune response of the body. Therefore, the polypeptide or the pharmaceutically acceptable salt thereof can be used for related detection of PD-1 and CTLA-4, and can be used as a new anti-tumor candidate drug, thereby providing a brand-new treatment scheme for cancer patients.

Antibodies that target VZV glycoprotein E (gE) bind to recombinant gE with high affinity, bind to gE on the surface of VZV infected cells, interact with immune system effectors (e.g., Fc receptors), mediate antibody-dependent cellular cytotoxicity (ADCC) as well as Antibody Dependent Cellular Phagocytosis (ADCP), and prevent VZV infection of cells.

The present invention relates to polypeptides which are covalently bound to aromatic molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of PD-L1. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and / or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by PD-L1.

The present invention relates to immunoglobulins that bind IgE and FcγRIIb with high affinity, said compositions being capable of inhibiting cells that express membrane-anchored IgE. Such compositions are useful for treating IgE-mediated disorders, including allergies and asthma.

The present invention relates to polypeptides which are covalently bound to non-aromatic molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of the Eph receptor tyrosine kinase A2 (EphA2). The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and / or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder characterised by overexpression of EphA2 in diseased tissue (such as a tumour).

On one hand, the invention discloses an anti-FOLR1 single-domain antibody VHH-F01, the amino acid sequence of the VHH-F01 is as shown in SEQ ID NO: 2, and the gene sequence of the VHH-F01 is as shown in SEQ ID NO: 1. The invention also discloses an umbilical cord mesenchymal stem cell preparation, which is characterized in that the preparation introduces the single-domain antibody VHH-F01 targeting the human FOLR1 and the gene of the human Bcl-2 anti-apoptotic protein into umbilical cord mesenchymal stem cells together through a lentiviral vector to obtain a stable and high-expression cell population; vHH-F01 expressed on the membrane surface of the preparation can specifically recognize ovarian cancer cells highly expressed by FOLR1 and can be combined with the ovarian cancer cells highly expressed by FOLR1 with high affinity, and meanwhile, the survival ability of stem cells in a tumor microenvironment can be remarkably enhanced by intracellular highly expressed Bcl-2 protein. In-vitro and animal experiments show that the preparation has excellent targeting homing efficiency and remarkable tumor inhibition effect on ovarian cancer tissues, can effectively prolong the lifetime of model animals, and provides a novel efficient targeting treatment tool for cell therapy of ovarian cancer.

The invention provides an anti-Claudin18.2 humanized single-domain antibody and a preparation method of the anti-Claudin18.2 humanized single-domain antibody. Specifically, the invention provides a Claudin18.2-targeted single-domain antibody, a humanized antibody thereof, a derivative protein, a gene sequence for encoding the Claudin18.2-targeted single-domain antibody, and an expression vector and an expression system for producing the Claudin18.2-targeted single-domain antibody. The single-domain antibody has high specificity, is combined with Claudin18.2 with high affinity and is basically not combined with Claudin18.1, and the single-domain antibody provides a research and development basis for development of antibody drugs, antibody coupling drugs and multi-specific antibody drugs.

The invention provides a Trop2-combined nano antibody as well as a product and application thereof, and relates to the technical field of antibodies. The invention discloses a nano antibody specifically binding to Trop2 protein, and a VHH sequence and a corresponding CDR sequence of the nano antibody. The nano antibody has the capability of high-affinity binding to target protein, and the nano antibody subjected to humanized modification still keeps the high-affinity binding characteristic.

The invention provides a nucleic acid molecule capable of being combined with oxytetracycline in a high-affinity mode. The nucleic acid molecule can detect the oxytetracycline with high sensitivity after being labeled with a fluorescent dye. Nucleic acid molecules (SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5) capable of specifically recognizing oxytetracycline are used as affinity ligands, and sensitive detection of oxytetracycline is realized by using nucleic acid molecules marked with fluorescent dye. According to the detection method disclosed by the invention, the detection limit of oxytetracycline reaches nM level, and the sensitivity is high.

Disclosed herein is a method for obtaining antibody-producing cells that express antibody molecules exhibiting high binding affinity to an antigen, comprising: contacting a population of antibody-producing cells, including cells expressing antibody molecules against an antigen on their cell surface, with a first labeled form of the antigen to enable the antigen to bind to antibody molecules on the cell surface; subsequently contacting the cells with (i) an unlabeled form of the antigen, (ii) a second labeled form of the antigen, or (iii) both the unlabeled and second labeled forms of the antigen; and collecting cells that remain bound to the first labeled form of the antigen, thereby obtaining cells that express antibody molecules with high affinity to the antigen. This method makes it possible to obtain cells expressing high-affinity antibody molecules from a pool of antibody-producing cells expressing antibody molecules with different affinities.

The present invention relates to polypeptides which are covalently bound to non-aromatic molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of PD-L1. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and / or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by PD-L1.

The invention relates to the technical field of biological pharmacy, and provides a double-target inhibition polypeptide or pharmaceutically acceptable salt and application thereof, the polypeptide comprises an amino acid sequence: TASPILYQMCCDYKR, and an amino acid fragment: X1WGIX2HSHFTHTX3WKX4 (I) with a structure as shown in a formula (I) is connected to the C tail end of the sequence. The polypeptide or the pharmaceutically acceptable salt thereof can generate high-affinity binding with PD-1 and CTLA-4 at the same time, has excellent biological blocking activity, can significantly improve the proportion of effector T cell subsets in tumor tissues, and effectively enhances the anti-tumor immune response of a body. Therefore, the polypeptide or the pharmaceutically acceptable salt thereof can be used for related detection of PD-1 and CTLA-4, can also be used as a novel anti-tumor candidate drug, and provides a brand new treatment scheme for cancer patients.

Provided is the use of a pyrrolidone derivative in the preparation of a GPI small-molecule inhibitor. The pyrrolidone derivative has a chemical structural formula as represented by formula (I): formula (I). The pyrrolidone derivative binds to GPI with high affinity and specifically inhibits GPI activity, thereby modulating the metabolism, particularly lactate accumulation, in a tumor microenvironment. The pyrrolidone derivative not only significantly enhances the killing effects of immune cells against tumor cells, but also potentiates the efficacy of an immunotherapeutic agent as an adjuvant drug, thereby enhancing the efficacy of tumor immunotherapy. The pyrrolidone derivative can be widely used in the field of tumor immunotherapy.

This invention discloses a nanobody and its application in the preparation of drugs for the treatment or diagnosis of CD176-positive tumor cancer. The nanobody sequentially comprises a CDR1 region, a CDR2 region, and a CDR3 region. The amino acid sequence of the CDR1 region is shown in SEQ ID No. 6, the amino acid sequence of the CDR2 region is shown in SEQ ID No. 7, and the amino acid sequence of the CDR3 region is shown in SEQ ID No. 8. This invention reveals that the nanobody possessing the above three complementarity-determining regions can bind to the CD176 protein (EC176) with high affinity. 50 With a molecular weight of 18.65 nM, it has the characteristics of small molecular weight, low immunogenicity, better solubility and stability, and can effectively detect the expression of CD176 or inhibit the activity of CD176, which has potential value in the detection and treatment of tumors.

Provided are antibodies or antigen binding polypeptides characterized by the ability to neutralize respiratory syncytial virus (RSV). Specifically, the antibodies or antigen binding polypeptides are characterized by high affinity binding to RSV fusion glycoprotein (RSVF). Further provided are methods for their identification, isolation, generation, preparation, and use, as well as the heavy chain and light chain sequences of the antibodies provided.

The present invention relates to polypeptides which are covalently bound to non-aromatic molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of the Eph receptor tyrosine kinase A2 (EphA2). The invention also relates to pharmaceutical compositions comprising said peptide ligands and to the use of said peptide ligands in preventing, suppressing or treating a disease or disorder characterised by overexpression of EphA2 in diseased tissue (such as a tumour).

The invention relates to application of Chinese yam protein, in particular to application of Chinese yam active protein in preparation of medicine for regulating blood testis barrier to treat testis dysfunction. L-YP has unique fluorescence characteristics and remarkable antioxidant activity, and can effectively improve testis immune microenvironment disorder by repairing blood testis barriers and inhibiting NLRP3 and TLR4 / MyD88 / NF-kappa B inflammatory pathways. In combination with a molecular docking technology, a molecular mechanism that key components such as YP2 (mitochondrial ornithine aminotransferase) and the like realize immunoregulation through high-affinity binding is clarified for the first time. According to the application disclosed by the invention, a molecular docking technology is creatively combined with system experimental analysis, and a molecular mechanism of improving testis injury by the Chinese yam protein is illuminated from the perspective of a'structure-function-target 'synergistic effect, so that a novel dietary intervention strategy is provided for preventing reproductive toxicity caused by chemotherapy; the application potential of medicinal and edible components in the field of male reproductive health is highlighted.

This invention discloses a nanobody that specifically binds to the CD176 protein and its applications. The nanobody sequentially comprises a CDR1 region, a CDR2 region, and a CDR3 region. The amino acid sequence of the CDR1 region is shown in SEQ ID No. 6, the amino acid sequence of the CDR2 region is shown in SEQ ID No. 7, and the amino acid sequence of the CDR3 region is shown in SEQ ID No. 8. This invention reveals that the nanobody possessing the above three complementarity-determining regions can bind to the CD176 protein (EC176) with high affinity. 50 With a molecular weight of 8.617 nM, it has the characteristics of small molecular weight, low immunogenicity, better solubility and stability, and can effectively detect the expression of CD176 or inhibit the activity of CD176, which has potential value in the detection and treatment of tumors.

The invention relates to the technical field of biological pharmacy, and provides a polypeptide capable of inhibiting PD-1 and CTLA-4 at the same time or a pharmaceutically acceptable salt of the polypeptide and application of the polypeptide, and the polypeptide has a structure as shown in a formula (I): TASPILYQMX1CDYKRCVX2VX3NGX4 (I). The polypeptide or the pharmaceutically acceptable salt thereof can generate high-affinity binding with PD-1 and CTLA-4 at the same time, has excellent biological blocking activity, can significantly improve the proportion of effector T cell subsets in tumor tissues, and effectively enhances the anti-tumor immune response of a body. Therefore, the polypeptide or the pharmaceutically acceptable salt thereof can be used for related detection of PD-1 and CTLA-4, can also be used as a novel anti-tumor candidate drug, and provides a brand new treatment scheme for cancer patients.

The invention belongs to the technical field of medicines, and particularly relates to application of traditional Chinese medicine active ingredients in antianaphylaxis, in particular to application of rare ginsenoside Rh1 in preparation of medicines for preventing or treating anaphylaxis. According to the invention, the action mechanism of Rh1 in resisting anaphylaxis is systematically clarified by integrating network pharmacology, molecular docking, molecular dynamics simulation and transcriptomics technologies for the first time. The Rh1 acts on four key host targets, namely ALB, CASP3, NFKB1 and STAT3 at the same time, regulates and controls an MAPK signal channel, a Th17cell diffusion channel and a PI3K-Akt signal channel, and synergistically exerts the dual effects of inhibiting allergens from invading host cells and relieving cytokine storm. The Rh1 and the four key targets all have high affinity binding. The invention provides a brand new theoretical basis and a clear mechanism support for developing Rh1-based broad-spectrum, high-efficiency and low-toxicity anti-anaphylaxis drugs.

The invention relates to polypeptide of a targeted tumor marker MUC1 and application of the polypeptide, and belongs to the technical field of nano medicine and biological materials. The sequence general formula of the polypeptide from the N terminal to the C terminal is X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13, x1, X2 and X3 are hydrophilic amino acids, X4-X12 are combinations of leucine, glutamine, isoleucine, threonine and lysine, and X13 is a hydrophobic amino acid. The polypeptide not only can be combined with a target spot with high affinity, but also can be self-assembled into a zigzag nanoflower, so that recognition residues of the polypeptide are functionally arranged on the surface of the nanoflower. The serrated polypeptide nanoflower can be used as a therapeutic drug in the aspect of tumor treatment, and can also be used as a delivery carrier.

Described herein are bicyclic peptides which are high affinity binders of programmed cell death 1 ligand 1 (PD-L1). Also provided are drug conjugates comprising the peptides described herein conjugated to one or more effector and / or functional groups. Also provided are pharmaceutical compositions comprising the peptides and drug conjugates described herein, and methods of using the peptide ligands and drug conjugates described herein for treating diseases mediated by PD-L1.

The application discloses a nucleic acid aptamer capable of combining with MPN-372 protein, and the sequence of the nucleic acid aptamer is shown as SEQ ID NO. 1-SEQ ID NO. 6. The nucleic acid aptamer has small molecular weight, stable chemical properties, is easy to preserve and label, and can combine with MPN-372 protein with high affinity by improving screening conditions. The nucleic acid aptamer is measured by surface plasmon resonance (SPR) and spot hybridization experiments to have high affinity and high specificity, and can be used in detection, diagnosis, imaging and treatment and the like, and has a wide application prospect.