181 results about "High affinity binding" patented technology

The invention discloses a monoclonal antibody targeting all CD45 subtypes and application of the monoclonal antibody, and belongs to the field of monoclonal antibody preparation. The hybridoma cell strain capable of stably secreting all anti-human CD45 subtype antibodies is successfully obtained by stably expressing short and long molecular subtypes of human CD45 extracellular regions in L929 mouse fibroblasts, immunizing BALB / c mice with L929 cells expressing the two molecular subtypes of human CD45, and fusing splenocytes with SP20 myeloma cells after the serum titer reaches the standard. And the monoclonal antibody targeting all subtypes of CD45 is obtained. The monoclonal antibody provided by the invention shows a high-affinity binding characteristic with all human CD45 molecular subtypes, has important application value in the aspect of human CD45 molecular detection, and can be used as a therapeutic antibody in the fields of tumor immunotherapy, autoimmune disease treatment, transplant rejection resistance and the like.

Provided are an anti-albumin antibody or an antigen-binding fragment thereof and the use thereof, and an anti-albumin nanobody with improved affinity or an antigen-binding fragment thereof. The anti-albumin antibodies or antigen-binding fragments thereof can bind to albumins from different species with high affinity. In addition, the anti-albumin antibody can be linked to a bioactive effector molecule to form a fusion construct without affecting the activity of the bioactive effector molecule.

The invention belongs to the technical field of antibodies, and particularly relates to an antibody and an antibody pair for resisting human IL-12 / IL-23p40 protein, and application of the antibody and the antibody pair. The antibody is a first antibody or a second antibody, amino acid sequences of light chains CDR1-3 of the first antibody are respectively shown as SEQ ID NO.3-5, and amino acid sequences of heavy chains CDR1-3 of the first antibody are respectively shown as SEQ ID NO.8-10; the amino acid sequences of light chains CDR1-3 of the second antibody are respectively as shown in SEQ ID NO.13-15, and the amino acid sequences of heavy chains CDR1-3 of the second antibody are respectively as shown in SEQ ID NO.18-20. The two antibodies disclosed by the invention have specific recognition and high-affinity binding capacities on recombinant and natural human IL-12 / IL-23p40 protein, and have important practical values in the fields of immunodiagnosis and immunotherapy taking p40 as a target spot.

The present invention relates to polypeptides which are covalently bound to 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 membrane type 1 metalloprotease (MT1-MMP). The invention also describes drug conjugates comprising said peptides, conjugated to one or more effector and / or functional groups which have utility in imaging and targeted cancer therapy.

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 present invention relates to compounds which can bind to KLHDC2 (Kelch Domain-Containing Protein 2) E3 ubiquitin ligase with high-affinity, and bifunctional degraders containing such compounds.

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 invention discloses a nucleic acid aptamer capable of simultaneously identifying neonicotinoid pesticide imidacloprid and clothianidin and application of the nucleic acid aptamer. The nucleic acid aptamer is XQ-20 or XQ-20.1, and the nucleotide sequence of the XQ-20 is as shown in SEQ ID NO.2; the nucleotide sequence of the XQ-20.1 is as shown in SEQ ID NO. 1. The nucleic acid aptamer disclosed by the invention can be simultaneously combined with imidacloprid and clothianidin in a high affinity manner, and has the advantages of low immunogenicity, batch synthesis, good biocompatibility and stability, small molecular weight, easiness in storage and the like.

The invention discloses a medicinal and edible active component-small molecule peptide-nano-selenium synergistic anti-aging composition screened based on a molecular docking technology, and belongs to the technical field of functional foods and biological medicines. The composition comprises an active ingredient with homology of medicine and food, a specific molecular polypeptide Ala-Val-His-Leu-Cys-Gly-Phe-Asp-Glu-Ser-Thr-Lys-Arg-Tyr-Pro and nano-selenium, wherein the active ingredient with homology of medicine and food is screened by a molecular docking technology and is combined with senescence-related targets Nrf2 and / or SIRT1 in a high affinity manner, and the active ingredient, the specific molecular polypeptide and the nano-selenium form an active ingredient-molecular polypeptide-nano-selenium ternary complex with homology of medicine and food. The preparation method comprises the following steps: screening the medicinal and edible active ingredients meeting conditions, preparing the molecular polypeptide, mixing the medicinal and edible active ingredients to form a compound, adding the nano-selenium, stirring and combining, and freeze-drying to obtain a finished product. The composition can be prepared into an oral preparation or an external preparation, has a multi-dimensional synergistic efficient anti-aging effect of an active ingredient targeted activation pathway, direct anti-oxidation of nano-selenium and enhanced delivery of a peptide carrier, and is suitable for preparation of anti-aging drugs or functional foods.

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 invention discloses a nanometer antibody of mycobacterium tuberculosis early secretory protein ESAT-6 and application thereof, relates to the technical field of antibody recombination and genetic engineering antibodies, and is characterized by providing two nanometer antibodies AEN1 and AEN5 which are derived from a total synthesis alpaca nanometer antibody yeast display library and are combined with ESAT-6 in high affinity, DNA sequences for coding the AEN1 and the AEN5, a carrier containing the DNA, a carrier containing the carrier containing the DNA, and a carrier containing the carrier containing the carrier containing the DNA. The invention relates to a vector, a host cell containing the vector, and a method for preparing AEN1 and AEN5 by utilizing genetic engineering. And the method for quantitatively detecting the ESAT-6 by using the double-antibody sandwich ELISA is established. Detection on clinical specimens of tuberculosis shows that the sensitivity of the diagnosis method is 94.9%, and the specificity is 100%. The antibody is used for preparing gold-labeled rapid test paper, and the ESAT-6 can be rapidly detected from serum of a mycobacterium tuberculosis infected patient.

The present invention relates to a bispecific anti-tumor antigen / anti-HSG antibody having screened light and heavy chain variable domains, which is capable of improving the pre-targeting of tumors for the specific delivery of therapeutic or diagnostic agents. The antibodies have a significant affinity for tumor antigens and stay at desired sites for a sufficient time. Antibodies that do not bind to the antigen can be rapidly cleared from the body, minimizing exposure of normal tissue. A humanized anti-HSG antibody is bound to each of a group containing histamine-succinyl-glycine (HSG) and a tumor antigen with high affinity. The bispecific antibodies can be further Fc silenced, resulting in additional properties, such as reduced binding to Fc [gamma] R and FcRn, thereby modulating effector function and regulating half-life. These antibodies are useful in the diagnosis and treatment of subjects suffering from malignancies.

The invention discloses a nano antibody specifically combined with CD176 protein and application thereof, the nano antibody sequentially comprises a CDR1 region, a CDR2 region and a CDR3 region, the amino acid sequence of the CDR1 region is shown as SEQ ID No.6, the amino acid sequence of the CDR2 region is shown as SEQ ID No.7, and the amino acid sequence of the CDR3 region is shown as SEQ ID No.8. The invention further discloses a preparation method of the nano antibody specifically combined with the CD176 protein and application of the nano antibody specifically combined with the CD176 protein. The invention discovers that the nano antibody with the three complementary determining regions can be combined with CD176 protein (EC50 is 8.617 nM) with high affinity, has the characteristics of small molecular weight, small immunogenicity, better solubility and stability and the like, can effectively detect the expression of CD176 or inhibit the activity of CD176, and has potential value in the aspects of tumor detection and treatment.

The invention belongs to the field of biological medicines, and particularly relates to a specific binding protein of IL-4R as well as a preparation method and application of the specific binding protein. The invention provides a specific binding protein of IL-4R, which has specific CDRs, can be bound with human IL4R alpha in a high affinity manner, and can block the interaction of IL4R alpha-IL4 / IL13-IL13R alpha1 and the corresponding intracellular signal transduction and biological effect.

Provided is relating to the field of disease treatment, and in particular, to an anti-CDH3 antibody or an antigen-binding fragment thereof, a nucleic acid molecule encoding the same and a method for preparing the same. The anti-CDH3 antibody or the antigen-binding fragment thereof has high affinity binding and endocytosis activities for CDH3, while exhibiting high specificity. Provided is furtherly relating to the use of the antibody or the antigen-binding fragment thereof in the treatment and diagnosis of diseases.

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.

The invention relates to a monoclonal antibody capable of specifically recognizing a tumor-associated antigen PZR as well as a preparation method and application of the monoclonal antibody. The anti-PZR monoclonal antibody can specifically recognize natural PZR protein expressed by triple negative breast cancer cells, and can realize high-affinity binding with recombinant PZR extracellular domain protein. The compound also has the capability of remarkably inhibiting migration and metastasis of PZR positive triple negative breast cancer cells, and has the characteristic of repression function. The anti-PZR monoclonal antibody provided by the invention can be used for preventing and treating PZR positive triple negative breast cancer metastasis, and is suitable for developing antibody drugs for targeted therapy of PZR positive tumors.

Provided are multivalent D-peptide compounds that specifically bind to a protein of interest. The multivalent D-peptide compounds may include two or more different variant D-peptide domains linked via a linking component. The D-peptide compounds may include a plurality of different domains that specifically bind to different binding sites on a protein of interest to provide high affinity binding to and potent activity against the protein of interest. Also provided are D-peptide variant GA domain polypeptides and D-peptide variant Z domain polypeptides having a Specific Determining Motif (SDM) for specific binding to a protein of interest, such as VEGF-A or PD-1. In some embodiments in which the protein of interest is a homodimeric protein of interest (e.g., VEGF-A, PD-1), the D-peptide compounds may be similarly dimeric and include dimers of multivalent (e.g., divalent) D-peptide compounds. Methods of using the compounds are provided, including methods of treating a disease or condition associated with a protein of interest in a subject.

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 invention discloses a group of nucleic acid aptamers specifically combined with CD8 molecules and application of the nucleic acid aptamers. The invention provides a nucleic acid aptamer of a targeted CD8 molecule. The nucleic acid aptamer comprises a core structure consisting of two stem loops, a multi-branch loop and a main stem; the multi-branch ring is positioned between the two stem rings; in the two stem loops, the stem loop close to the 5'end is composed of a random base sequence, the stem loop close to the 3 'end is composed of GC paired bases, and the loop structure is formed by a fixed sequence AGCTTGAAAT; the multi-branch ring is provided with a fixed base GTGA; the main stem is formed by pairing random basic groups. According to the method, a machine learning clustering method is adopted to identify a core region in an aptamer family, and secondary structure analysis is performed, so that a common structure capable of being specifically combined with CD8 protein is successfully found, the truncation and optimization process of an aptamer candidate library is simplified, the design of a novel aptamer is also promoted, and the method is suitable for large-scale popularization and application. These aptamers are capable of binding to CD8 proteins with high specificity and high affinity.

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 invention belongs to the field of medicinal chemistry, and particularly relates to a method for screening a compound for treating atrial fibrillation and application. Comprising the following steps: (1) selection and pretreatment of a CaMK II delta crystal structure; (2) selecting the center of a butt-joint box and setting the size of the butt-joint box to generate the butt-joint box; (3) selecting and downloading a to-be-screened compound library; (4) performing docking calculation by adopting a molecular docking algorithm in molecular docking software according to the docking box and the to-be-screened compound library, and retaining the first 10% of compounds with higher docking scores; (5) treating the compounds which are 10% before docking scoring by using a Lipinski class drug five rule, and excluding the compounds which are low in drug-likeness; and (6) carrying out ADMET property prediction on the compounds conforming to the drug-like V rule, and screening the active compounds under the conditions. According to the invention, on the basis of analysis and virtual screening of AI on a large amount of compound data, the compounds obakurol A and urolithin C with high affinity binding characteristics with atrial fibrillation related target CaMKII delta are obtained, and calcium ion homeostasis in myocardial cells can be effectively regulated.

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.