61 results about "Cathepsin B" patented technology

The invention discloses a cathepsin B activated fluorescent probe which comprises a dicyanoisosulfone fluorescent report unit and a cathepsin B specific restriction enzyme cutting site GFLG peptide chain. When CTSB specifically cuts a GFLG peptide chain, a DCO molecule with an amino group with relatively strong electron donating ability is generated, so that the fluorescence emission behavior of the probe is rapidly activated through a one-step enzyme catalysis reaction. The invention also provides a preparation method of the cathepsin B activated fluorescent probe. The invention also provides a nano particle for packaging the cathepsin B activated fluorescent probe, and the nano particle is simple in preparation process and mild in reaction condition. The cathepsin B activated fluorescent probe is prepared into nanoparticles, and the nanoparticles can realize accumulation of the material in tumor tissues and accurate imaging in apoptotic tumor cells by enhancing the permeation retention effect, have better biocompatibility and can be used for detecting the apoptotic tumor cells.

The invention discloses a Jinhua ham taste optimization method based on metabonomics and an enzyme activity regulation and control technology. The method belongs to the field of meat quality control, and comprises the following optimization steps: carrying out sensory scoring on samples in different processing stages, and carrying out non-targeted analysis by using hydrophilic interaction liquid chromatography and MS / MS; analyzing and mining the metabonomics data; screening out differential metabolites in the processing process by applying a significance analysis p value, a difference multiple and a variable weight value; combining activity change results of cathepsin B and cathepsin L in the processing process; the activity of cathepsin B and cathepsin L is regulated and controlled by using a PF-DBO optimization algorithm, samples are collected and analyzed, and the influence of enzyme activity change and the change of the enzyme activity change on the content of the characteristic taste marker are evaluated. By precisely regulating and controlling the activity of cathepsin B and cathepsin L, the problem of complex relationship between taste substance change and cathepsin activity in the Jinhua ham processing process is solved; the control strategy enables the overall quality of the Jinhua ham to be significantly improved.

The invention discloses a polypeptide, a polypeptide / siRNA compound and application thereof, and belongs to the field of biological medicine preparations. The amino acid sequence of the polypeptide disclosed by the invention is as follows: Nap-FFKYGFRRGHHHHRHHHR or Nap-FFKYGFRRGHHHHKHHK. A polypeptide / siRNA compound formed by the polypeptide and siRNA is uniform in particle size and good in stability, the hydrophobic end of the polypeptide / siRNA compound can respond to cathepsin B in lysosome to be assembled into nanofibers, a membrane of the lysosome is damaged, and then escape of the lysosome of the siRNA is promoted; after the siRNA / cationic peptide part is released into cytoplasm, the cationic peptide responds to the change of cytoplasm pH to reduce the electropositivity of the siRNA molecule, so that efficient cytoplasm delivery of the siRNA molecule is realized, and the siRNA molecule is promoted to play a silencing effect. The embodiment of the invention shows that the Pep / siRNA compound disclosed by the invention has relatively strong in-tumor retention capacity in a mouse body and can effectively inhibit the growth of breast cancer tumors.

The invention discloses an electrochemical urine biopsy system for cathepsin B analysis and a detection method of the electrochemical urine biopsy system. The electrochemical urine biopsy system comprises gold nanoparticles AuNPs, a peptide-peptide nucleic acid PNA series probe and an electrochemical sensor. The peptide-peptide nucleic acid tandem probe is combined with gold nanoparticles through a mercaptan modified sequence to form a spherical nanostructure with the diameter of 15 nm, a polypeptide substrate sequence serves as a specific reaction substrate of cathepsin B, and PNA provides stability and a signal shielding function. The electrochemical sensor is based on a cutting enzyme-assisted DNAwalker mechanism, signal amplification is started through methylene blue MB release, and high-sensitivity detection of the released PNA probe is achieved. The system provided by the invention has the characteristics of high specificity, high sensitivity and rapid response, can realize quantitative analysis of cathepsin B through noninvasive urine biopsy, and provides a new technical means for early diagnosis and treatment monitoring of tumors.

The invention belongs to the field of biological medicine, and relates to a human serum albumin covalent binding type targeted folate receptor micromolecule drug conjugate prodrug and application thereof. The prodrug disclosed by the invention has a structure as shown in a formula I, six-carbon maleimide is used as a site combined with endogenous albumin, and albumin is used as a carrier to deliver the drug. The prodrug can increase accumulation of the drug in tumors under the EPR effect. A dipeptide chain composed of valine and alanine is used as a cleavage site of cathepsin B, an adapter composed of p-aminobenzyl ether and N-methylamino-4-nitrophenol releases drugs in an acidic environment, an azidohexanoic acid structure is added to a side chain of p-aminobenzyl ether, so that the site of a targeting ligand can be increased, and SN38 is used as a small molecule cytotoxic load. The micromolecular prodrug has dual functions of active targeting and passive targeting, and can effectively improve the concentration in solid tumors, reduce toxic and side effects and improve the anti-tumor effect under the mediation of related receptors.

The invention discloses cell-penetrating peptide modified enzyme-sensitive PDC type PROTAC as well as a preparation method and application thereof, and belongs to the technical field of tumor targeted therapy. The cell-penetrating peptide modified enzyme-sensitive PDC type PROTAC is obtained by modifying a target protein ligand with a cell-penetrating peptide and an enzyme-sensitive Linker (GFLG) as an antitumor drug, has the capability of releasing the PDC type PROTAC under the catalysis of cathepsin B, has small influence on the cell activity of U251 cells, U87 cells and HEK293 cells, has proliferation inhibition activity on the U251 cells and the U87 cells, and can be used for preparing an antitumor drug. The polypeptide can degrade target proteins in U251 cells and U87 cells, can induce apoptosis of the U251 cells and the U87 cells, has an influence on the cycle of the U251 cells, can be used for preparing antitumor drugs (in the aspects of targeted protein degradation and membrane permeation), has a good application prospect in preparation of drugs targeting human brain glioma cells, and can be used in another important field of PROTAC drug development.

The invention relates to a radioactive metal labeled antibody obtained by labeling an antibody with a radioactive metal. A functional chelate linker is coupled to the antibody, and the functional chelate linker is provided with: a chelate part capable of coordinating with a radioactive metal ion; and a functional unit having a function of improving intracellular retention. It is preferable that the functional unit has a structure obtained by polymerizing ethyleneimine or ethylene glycol, or a structure capable of binding to cathepsin B. The functional unit preferably has a structure obtained by polymerizing ethyleneimine at a degree of polymerization of 1-7 (inclusive).

The invention provides an activatable semiconductor polymer as well as a preparation method and application thereof. The activatable semiconductor polymer disclosed by the invention can be efficiently accumulated at a tumor site, due to the existence of a side chain electron withdrawing group, the fluorescence of the polymer is in a quenched state, the fluorescence of the polymer is recovered after tumor markers such as biological mercaptans, active oxygen and cathepsin B are respectively responded, and accurate imaging and sonodynamic therapy can be carried out at the tumor site. Meanwhile, the activatable semiconductor polymer can mark immune cells (such as dendritic cells and macrophages) and track the process of transferring the immune cells from tumors to tumor drainage lymph nodes.

The invention discloses a glucan-based MMAE conjugate as well as a preparation method and application thereof, and relates to the technical field of medicines. The conjugate takes glucan with good biocompatibility as a carrier, and is covalently connected with a cytotoxic drug MMAE through a VC peptide linker capable of being cut by cathepsin B. The conjugate has good serum stability, can specifically release drugs at a tumor site, and realizes efficient tumor uptake by virtue of the stealth effect of glucan and potential GLUT1 targeting. In-vitro and animal experiments show that the conjugate has a remarkable treatment effect on pancreatic cancer and is low in systemic toxicity.

The invention provides novel compositions and methods for the treatment of Radiation-Induced Bystander Effects (RIBE), resulting from radiation exposure. In one preferred embodiment the inventions includes novel therapeutic agents, including but not limited to quercetin and quercetin analogs, as well as E64, CA074, CA074Me, that interfere with the activity of Cathepsin B.

This invention discloses an enzyme- and pH-responsive nucleic acid loading and delivery material and its preparation method. The material can be used for efficient loading and delivery of nucleic acid molecules. The preparation method uses amphiphilic zwitterionic monomers to improve the reverse emulsion polymerization system, enhancing polymerization at the two-phase interface and avoiding the extrusion effect of polymerization in the aqueous core on nucleic acid molecules, thereby improving the loading efficiency of nucleic acid molecules. Further preparation of cross-linking agents MP-CL and CB-CL, which can cleave in response to matrix metalloproteinase II or cathepsin B, endows the nanogel with the ability to respond to charge reversal in the tumor matrix and to release nucleic acid molecules from tumor cells. The acid-sensitive blocks on the amphiphilic monomers give the nanogel lysosomal escape capability. The delivery material can efficiently deliver nucleic acid molecules into cells and exhibits excellent stability and biosafety.

The invention discloses an albumin coupling medicine as well as a preparation method and application thereof. The cathepsin B response type camptothecin albumin coupling drug is innovatively designed and synthesized by taking albumin as a carrier, the albumin coupling drug has good cathepsin B response drug release capability, efficient tumor targeted delivery of the drug is realized, camptothecin is responded and released in tumor cell lysosome, and the drug delivery efficiency is improved. The specific anti-tumor effect is achieved. The invention provides a regulation and control method in the aspects of preparation, drug loading capacity and in-vitro release of the albumin coupled drug, size effects in the aspects of cellular uptake, cytotoxicity, tumor targeting and retention are illustrated, and guidance is provided for designing an efficient and safe tumor drug delivery system.

Compositions and methods are provided of a therapeutic nanoparticle composed of collagenase IV linked via a linker (e.g. cathepsin B cleavable linker) to ferumoxytol (iron oxide). The collagenase IV is key in the composition intended for the breakdown of the tumor wall as the collagenase. Such compositions and methods are aimed at solving at the same time two of the main challenges of current approaches in the treatment of glioblastoma multiforme (GBM) which are low specificity and poor uptake.

The invention discloses a cathepsin B activated chemiluminescent nanoparticle. The cathepsin B activated chemiluminescent nanoparticle is prepared from cat B-C-550, hypericin and DSPE-mPEG2000 (Distearoyl Phosphate Polyethylene-mPEG (Polyethylene Glycol) 2000 in a self-assembly manner; the structure of the cat B-C-550 is as shown in a formula I in the specification. The invention discloses an application of cat B enzyme activated chemiluminescent nanoparticles in preparation of reagents or drugs for screening or diagnosing tumors. The invention discloses an application of cat B enzyme activated chemiluminescent nanoparticles in preparation of a cancer imaging reagent and / or a medicine for treating tumors. According to the invention, chemiluminescence imaging and in-situ cancer PDT treatment without external exciting light are realized. The cat B enzyme response type chemiluminescent nanoparticles are high in stability and can be effectively targeted and enriched at tumor focus parts.

The invention discloses trichina cathepsin B as well as a coding gene and application thereof, and belongs to the technical field of gene engineering. According to the invention, a food-grade L.lactis expression system is utilized to construct a lactic acid bacteria expression system of a TsCB gene, after the L.lactis recombinant strain pNZ8149-TsCB / L.lactis NZ3900 is subjected to intragastric administration on a mouse, the body can be induced to generate 2-type immune response, the recruitment of M2-type macrophages is increased, the infiltration of neutrophil is reduced, and the expression of proinflammatory factors and inflammatory mediators is inhibited, so that the colitis of the DSS mouse is improved; and a foundation is laid for subsequent research and development of food-grade oral insect-derived molecular medicines for treating colitis.

The invention belongs to the field of biological medicine, and particularly relates to a nano-drug based on chondroitin sulfate as well as a preparation method and application of the nano-drug. Chondroitin sulfate (CS) and dasatinib (DAS) are connected through a GFLG connexon responded by cathepsin B (CTSB) to prepare the prodrug CS-GFLG-DAS (CGD), the prodrug CS-GFLG-DAS (CGD) is used for reversing the phenotype of cancer-related fibroblasts and reducing the biosynthesis of extracellular matrixes, fibrotic tumors are efficiently treated, and a new perspective is provided for optimizing the application of immunotherapy in fibrotic tumors.

The invention discloses a polypeptide coupling drug and a preparation method and application thereof, and belongs to the technical field of biological medicine, the polypeptide coupling drug is formed by bonding and connecting cyclic peptide molecules, connecting arms, spacers and antibiotic drugs through chemical bonds; aIP-III D4A amide and structural analogues of AIP-III D4A amide are selected as cyclic peptide molecules; the connecting arm selects a molecule which is sensitive to the specificity of cathepsin B in lysosome; and the spacer is a structural fragment capable of being automatically degraded. The polypeptide coupling drug has a good antibacterial effect, especially has an outstanding treatment effect on intracellular bacterial infection which is relatively difficult in current clinical treatment, and can be used for preparing efficient antibacterial drugs.

The invention relates to the field of biological medicine, in particular to an endoplasmic reticulum targeting peptide, an agonist, a preparation method and application. Wherein the agonist comprises an endoplasmic reticulum targeting peptide, and further comprises a mitochondrial membrane disturbing sequence and a sequence with cathepsin B response, the mitochondrial membrane disturbing sequence is KLAKLAK 2, and the sequence with cathepsin B response is GFLG; the endoplasmic reticulum targeting peptide comprises a KKKAA peptide sequence, and chlorin e6 and R8 peptide are connected to the KKKAA peptide sequence; the mitochondrial membrane disturbing sequence is connected to the R8 peptide through a sequence with cathepsin B response. According to the scheme, the characteristics of biochemical information interaction and tumor growth regulation of the mitochondria and the endoplasmic reticulum are utilized, excessive stress of the endoplasmic reticulum and a mitochondria calcium uptake channel are activated at the same time in a safe and controllable mode, free Ca < 2 + > in the endoplasmic reticulum rapidly flows into the mitochondria, the steady states of the endoplasmic reticulum and the mitochondria of tumor cells are damaged, and the tumor growth is controlled. And the two synergistically induce cells to start an apoptosis procedure, so that the aim of treating diseases is fulfilled.

The invention relates to a cathepsin B sensitive fatty acid-adriamycin prodrug as well as albumin nanoparticles, a preparation method and application thereof, and belongs to the technical field of medicines. The cathepsin B sensitive fatty acid-adriamycin prodrug is a prodrug as shown in a formula (I), a geometric isomer thereof, and pharmaceutically acceptable salts, hydrates and solvates thereof, wherein n is equal to 0-14. The invention also relates to a combined albumin nanoparticle prepared by entrapping the cathepsin B sensitive fatty acid-adriamycin prodrug by using human / bovine serum albumin as a carrier. The albumin nanoparticles are small in particle size and uniform in form, have good placement stability and colloidal stability, can stably exist in systemic circulation and normal tissues, and release a parent drug adriamycin after being taken by tumor cells and hydrolyzed by cathepsin B; therefore, specific killing of tumor cells is realized without generation of serious toxic and side effects, and good clinical development prospects are achieved.

The present invention provides the application of the secretory protein CTSB (cathepsin B) in predicting the risk of vascular lesions in patients with diabetic foot ulcers (DFUs), belonging to the field of biomedicine technology. Through single-cell sequencing studies, the present invention found that the secretory protein CTSB is significantly enriched in vascular endothelial cells in the blood vessels of DFU patients, with high PPI connectivity and low expression; CTSB overexpression / knockout experiments found that CTSB is associated with the proliferation and tubulogenesis of vascular endothelial cells in human blood vessels; ELISA experiments also found that the level of secretory protein CTSB in serum can be used as a marker for predicting the risk of vascular lesions in DFU patients, and that the expression level of CTSB is negatively correlated with the Wanger grade of diabetic foot; the method can predict the risk of peripheral vascular lesions in DFU patients, has the advantages of simple operation and high sensitivity, can reduce false detection and missed detection, and has stable and reliable test results, making it suitable for large-scale detection.

The present application relates to a freshness indicator protein related to quality traits of low-temperature stored Siniperca chuatsi, endogenous proteases and applications. The freshness indicator endogenous proteases are related to postmortem proteolysis and meat softening of Siniperca chuatsi, including cathepsin B, cathepsin L and calpain. The freshness indicator proteins are related to quality changes occurring during postmortem cold storage of Siniperca chuatsi, including myoactin 1, myosin binding protein, LDB protein, actin-related protein, etc. The present application determines the change rule of endogenous protease activity of Siniperca chuatsi at different storage stages, and the dynamic influence on muscle proteolysis and muscle degradation of Siniperca chuatsi, and reveals the internal relationship with fish meat sensory quality and processing characteristics, and clearly defines the "critical point" of quality deterioration of Siniperca chuatsi. It provides clear guidance for the control of endogenous enzyme-mediated quality deterioration in the processing and storage process of Siniperca chuatsi.

The present disclosure relates to a cancer-targeting peptide that can be cleaved by cathepsin B in cancer cells and is characterized by forming prodrug nanoparticles together with an anticancer agent, wherein the preparation of carrier-free prodrug nanoparticles may provide a new approach to cancer treatment and may significantly improve cancer targeting and the therapeutic efficacy of an anticancer agent.

The invention discloses a human leukemia cell targeted cell-penetrating peptide modified enzyme sensitive PDC type PROTAC as well as a preparation method and application thereof, and belongs to the technical field of tumor targeted therapy. The PDC type PROTAC is formed by connecting a hypoxia inducible factor 1 alpha (HIF-1alpha) protein fragment and imatinib through dodecanedioic acid, and is further modified through a human leukemia cell targeted cell-penetrating peptide Cyclo-C9C-R and a cathepsin B sensitive sequence GFLG. The modified PDC type PROTAC can release original drugs under the catalysis of cathepsin B, has small influence on THP1 cell activity, but can effectively inhibit proliferation of K562 cells and KU812 cells, degrade target proteins, induce cell apoptosis and influence cell cycles, so that the PDC type PROTAC has remarkable advantages in the aspect of preparation of antitumor drugs, and has broad application prospects. Particularly, the compound shows a good application prospect in the development of drugs for targeting human chronic myelogenous leukemia cells and human peripheral blood basophilic leukemia cells, and opens up a new field for the development of PROTAC drugs.

The invention relates to conjugates of biologically active compounds, wherein such a conjugate is comprised of a sequence of amino acids containing a tripeptide that confers selective cleavage by tumor tissue homogenate for release of free drug and / or improves biodistribution into the tumor tissue in comparison to normal tissue homogenate from the same species, wherein the normal tissue is the site of an adverse event associated with administration to a human subject in need thereof of a therapeutically effective amount of a comparator conjugate whose amino acid sequence is a dipeptide known to be selectively cleavable by Cathepsin B.

Populations of CAR T cells that exhibit reduced trogocytosis are disclosed, as well as methods for making such cells and methods of using such cells in the treatment of cancer. A reduction in trogocytosis is achieved by inhibiting Cathepsin B in the CAR T cells and / or inducing ubiquitylation of cancer antigens taken up by the CAR T cells.

The present invention concerns a particular crystalline freebase form of 2-(4-chlorobenzylamino)-4-(4-tert-butylaminopiperidin-1-yl)-quinoline. It also relates to a pharmaceutical composition and a kit of parts comprising such a crystalline freebase form and their use in treating and / or preventing cancers, fibrosis, autophagy and cathepsins B (CTSB), L (CTSL) and D (CTSD) related diseases.

The application discloses application of cathepsin E in preparation of a drug for treating or preventing lung cancer, relates to the technical field of biological medicine, and first proves that CTSE is highly expressed in lung adenocarcinoma tissues and has the biological function of inhibiting lung cancer cell proliferation through clinical sample analysis, cell function experiment and animal experiment. Mechanism research shows that CTSE plays the anticancer role by down-regulating the expression of cathepsin B (CTSB) and promoting the degradation of STING protein through a lysosome pathway and inhibiting the cGAS-STING natural immune pathway. The application clarifies the application value of CTSE as a new target for treating lung adenocarcinoma, provides a theoretical basis and experimental basis for developing a novel lung cancer treatment drug, and has an important clinical application prospect.

The invention relates to application of HDAC (histone deacetylase) inhibitor and Cathepsin B inhibitor combined medicine in lung cancer treatment, and belongs to the technical field of biological medicine. Research finds that histone deacetylase inhibitors (HDAC inhibitors, HDACIs) can promote invasion and migration of tumor cells by inducing epithelial-mesenchymal transition while inhibiting tumor growth, and side effects are generated. Therefore, in order to inhibit the side effect and enable the HDAC inhibitor to effectively exert the curative effect clinically, the invention provides a novel medicine combination mode, the HDAC inhibitor and the Cathepsin B inhibitor are combined for use, so that the antitumor activity of the HDAC inhibitor is retained, the tumor invasion and migration capability induced by the HDAC inhibitor is effectively inhibited, and the curative effect of the HDAC inhibitor is effectively exerted clinically. A new strategy is provided for precise treatment of solid tumors, and the method is verified in treatment of lung cancer.

The invention discloses an efficient fluorescein probe as well as a preparation method and application thereof, and relates to the field of fluorescein probes. The high-efficiency fluorescein probe prepared by the invention has an extremely low detection limit on cathepsin B, has excellent fluorescence performance and good biocompatibility, is suitable for detection of tumor-related cathepsin B, and has important application significance in the aspect of early diagnosis of tumors.

The invention provides a preparation method and application of a multi-target enzymatic self-assembly fluorescence activated nanoprobe, and belongs to the field of pharmacy. According to the method, an Fmoc solid-phase peptide synthesis strategy is adopted, an N end is connected with a fluorescence quencher Dabcyl, a C end is marked with fluorescein, a near C end is a self-assembly sequence Y (pY) YG capable of generating self-assembly behavior through dephosphorylation of alkaline phosphatase, and a middle section is a cleavage sequence KGGFLGK capable of being cleaved into a fluorescent'switch 'by cathepsin B; the near N end is a functional polypeptide F-pY-LyP-1 of a targeting sequence CGNKRTRGC or LyP-1 which can be highly combined with a p32 receptor on the surface of a foam cell. The fluorescence activated nanoprobe accurately reaches a plaque part under the synergistic effect of multiple target points and is self-assembled into spherical nanoparticles, so that the aggregation and retention effects of the probe in the plaque are improved, the non-specific signal interference is reduced, and the early atherosclerotic plaque is more accurately identified.