83 results about "Lysosomal targeting" patented technology

The invention discloses a lysosome targeted chimera based on Sortilin and application thereof. The lysosome targeted chimera comprises a ligand molecule of a lysosome targeted receptor and a ligand molecule of a targeted protein to be degraded, wherein the ligand molecule and the ligand molecule are connected through a linker; the lysosome targeting receptor is Sortilin, and the ligand molecule of the lysosome targeting receptor is a polypeptide targeting the Sortilin; the protein to be degraded is membrane protein or extracellular protein. Furthermore, the polypeptide of the targeted Sortilin is connected with an enzyme response sequence and an integrin receptor targeting sequence. According to the invention, the Sortilin-combined ligand neurotensin is functionally coupled with the neutralizing antibody or polypeptide of overexpression protein in targeted tumor or inflammatory diseases, and the Sortilin-combined ligand neurotensin has obvious treatment gain in malignant solid tumor and psoriasis models. The discovery promotes the transformation potential of the lysosome participating in the biological agent, and provides a dual strategy for realizing accurate degradation through receptor recruitment and microenvironment induction.

The present disclosure provides lysosomal targeting bifunctional molecules that target disease causing anti-TSHR autoantibodies for degradation. The lysosomal targeting bifunctional molecules include a ligand moiety that specifically binds to an asialoglycoprotein receptor (ASGPR), and which is linked via a carrier protein to a thyroid stimulating hormone receptor (TSHR) polypeptide that specifically binds target anti-TSHR autoantibodies.

Provided herein is disclosure of a recombinant bifunctional protein or polypeptide capable of binding to a cell surface receptor for lysosome targeting that is made up of an N-glycosylated peptide comprising at least one N-glycan group and a protein of interest, or antibody or antibody fragment capable of binding to a protein of interest. Also provided herein are methods for producing said recombinant bifunctional protein. Also provided herein are methods for lysosomal degradation of a protein of interest comprising introducing to a cell the peptide sequence of the recombinant bifunctional protein.

The application discloses a LYTAG-Gem compound for enhancing the anti-tumor effect of gemcitabine and application thereof, relates to the technical field of biological medicine, and particularly relates to a gemcitabine (Gem) targeted delivery system based on a lysosome targeting chimera (LYTAC) and application thereof in enhancing the anti-tumor process. 2+ The system is assembled from heavy chain ferritin, Ni 2+ , NTA-PEG5000-DBCO and a targeting ligand TPP-1-N3 in a specific mass percentage, can efficiently load Gem and form a nano compound with a particle size of about 59-79 nm, the system targets tumor cells through heavy chain ferritin, and realizes site-specific release of Gem in cells by means of an endocytosis-lysosome pathway mediated by the LYTAC structure, in-vivo pharmacodynamic experiments show that the LYTAC-Gem compound can significantly inhibit the tumor growth of a KPC pancreatic cancer mouse model, molecular mechanism research further reveals that the LYTAC-Gem compound can down-regulate the expression of PD-L1 protein in tumor tissues, and it is indicated that the LYTAC-Gem compound has the potential to activate an anti-tumor immune response, and the application provides a novel targeted delivery strategy for overcoming the toxic side effects and tumor drug resistance of gemcitabine.

The invention discloses a lysosome targeted degradation system based on a DNA phase separation aggregate as well as a preparation method and application of the lysosome targeted degradation system, and belongs to the technical field of biological medicine and nanotechnology. The lysosome targeted degradation system based on the DNA phase separation aggregate comprises an RNA-DNA tetrahedral framework with a cohesive end, the RNA-DNA tetrahedral framework is formed by self-assembly of a core chain and an edge chain through complementary base pairing, the edge chain is a DNA-RNA chimeric oligonucleotide chain, and the DNA-RNA chimeric oligonucleotide chain is a DNA-RNA chimeric oligonucleotide chain. One or more sections of RNA ribonucleotide sequences which can be specifically recognized and cut by RNase H enzyme are embedded in the sequence, and the tail end of the RNA ribonucleotide sequence is modified with a cohesive tail end for driving phase separation and a cell membrane anchoring group; the RNA-DNA tetrahedral framework is modified with an aptamer of a targeted membrane protein. After entering cells, the system is subjected to liquid-liquid phase separation in a lysosome acid environment through interaction of cohesive ends, a micron-sized large-size aggregate is formed in situ, the residence time of a nano-drug in the lysosome is prolonged, and efficient degradation of target membrane protein is realized.

This invention discloses a naphthimide-based fluorescent probe for detecting HClO and its preparation method. The fluorescent molecular probe uses naphthimide as the fluorophore and C=N as the specific reaction site for HClO. Due to the presence of the naphthimide fluorophore, the probe molecule exhibits two-photon properties, enabling deep tissue penetration, reducing background noise, and facilitating fluorescence imaging of biological systems. Furthermore, the introduced morpholine group allows for lysosomal targeting, enabling the monitoring of hypochlorous acid concentration levels in lysosomes, making it a valuable tool for early disease diagnosis. In addition, this type of probe molecule is simple to synthesize, operates under mild reaction conditions, exhibits stable optical properties, and has a high synthesis yield. It can detect a wide range of HClO, making it practically valuable in fields such as biochemistry and environmental science.

The invention relates to the technical field of biological medicine, in particular to application of hordenine in preparation of a lysosome targeting preparation. The hordenine can be captured by the lysosome and accumulated in the lysosome, so that the hordenine has the characteristic of targeting the lysosome, and the hordenine can be used for preparing the lysosome targeting preparation. Hordenine is small in toxic and side effects and high in safety, and the problems that existing lysosomal targeted compounds such as chloroquine are high in toxicity and narrow in therapeutic window are effectively solved.

The application discloses application of a lipoic acid analogue in preparation of a product for relieving myocardial cell hypertrophy, and the lipoic acid analogue DMAE-LA is N -(2-(dimethylamino)ethyl)-5-(1,2-dithiopentyl-3-yl)valeric amide. DMAE-LA can effectively reduce ISO-induced myocardial hypertrophy of mice, reduce heart weight index and ANP and BNP expression, and significantly improve heart function. A small dose (2-10 μM) of a lysosome-targeting lipoic acid analogue DMAE-LA can effectively improve Ang II-induced myocardial hypertrophy and oxidative stress in H9c2 cells, and the protective effect is better than that of a high dose (200-400 μM) of LA. As a new substitute of traditional LA, DMAE-LA shows great potential for prevention and treatment of cardiovascular diseases.

The present invention belongs to the field of medicinal chemistry technology and relates to a lysosomal-targeted nitroreductase-responsive fluorescent probe based on a triphenylamine backbone, its synthesis method, and its application. The triphenylamine derivative-based lysosomal-targeted nitroreductase-responsive fluorescent probe provided by the present invention does not emit light upon initial entry into cells. However, after a period of culture in cancer cells, the electron-withdrawing nitro group is reduced by the intracellular nitroreductase. Under laser irradiation, the charge within the fluorophore shifts, resulting in fluorescence. The present invention also provides a method for synthesizing the lysosomal-targeted nitroreductase-responsive fluorescent probe and its use in bioimaging.

To provide a means capable of inducing decomposition of a new protein which can be comprehensively and generally used for all cells.SOLUTION: A peptide compound comprising a target-binding moiety, a cell membrane-penetrating peptide moiety, and a lysosome-inducing peptide moiety.SELECTED DRAWING: None

The present invention belongs to the field of chemical analysis and detection technology, and provides a pyrazoline derivative lysosome-targeted biological thiol fluorescent probe and its preparation method and application. The preparation method of the pyrazoline derivative lysosome-targeted biological thiol fluorescent probe of the present invention comprises the following steps: mixing compound 1, 2-chloro-3,5-dinitropyridine, a base and an organic solvent and reacting to obtain a pyrazoline derivative lysosome-targeted biological thiol fluorescent probe. The fluorescent probe of the present invention can monitor the concentration fluctuations of Cys, Hcy and GSH in living cell lysosomes in real time by fluorescence imaging, and has the advantages of high selectivity, high sensitivity and rapid response; good selectivity and low cytotoxicity make it an ideal tool for simultaneous detection of Cys, Hcy and GSH.

This invention relates to a lysosome-targeting fluorescent dye based on the BODIPY structure and its synthesis method, belonging to the field of organic fluorescent dyes. The invention designs and synthesizes the lysosome-targeting fluorescent dye BDP. The dye molecule uses BODIPY as the parent structure, and a novel lysosome-targeting fluorescent dye molecule is synthesized by introducing diphenylphosphine salt and tert-butyloxycarbonyl groups. The synthetic route of this dye is simple, it possesses excellent photostability, and exhibits good resistance to interference from ions, amino acids, and viscosity. Furthermore, this dye demonstrates superior fluorescence performance in a variety of common solvents, with fluorescence quantum yields exceeding 0.70. Experimental results show that this fluorescent dye can precisely target lysosomes in living cells, demonstrating promising applications in the field of bioimaging.

The application discloses a kind of strong electron donor triphenylamine modified coumarin dyes, its synthesis method and application;The dye has blue-green light excitation characteristics, the maximum absorption wavelength is 415-425 nm, the maximum emission wavelength is 495-505 nm, and excellent lysosome targeting and positioning ability is shown.It overcomes the problem of low efficiency of traditional coumarin as photosensitizer in molecular structure design, realizes the efficient I type photodynamic effect, can generate active oxygen under light efficiently.In addition, this dye has good cell membrane permeability and low dark toxicity, suitable for biomedical imaging, photodynamic therapy of tumor and other fields.The synthesis method is simple, raw materials are easy to obtain, and the yield is high, suitable for large-scale production.Experiments show that the dye can effectively enrich in cell lysosomes, realize precise killing of cancer cells, and show great potential in cancer diagnosis and treatment integration.

Provided herein are antigen-binding proteins (ABPs) that selectively bind to M6PR and its isoforms and homologs, and compositions comprising the ABPs. Also provided herein are bispecific antigen-binding proteins (ABPs) that selectively bind to internalizing receptors, and a soluble target molecule or cell surface target molecule and its isoforms and homologs, and compositions comprising the ABPs.

The invention belongs to the technical field of biomedical detection, and relates to a quinoxaline-derived Aza-BODIPY AIE fluorescent probe, the probe is composed of three parts of fluorophore Aza-BODIPY, rotor benzothiazole and lysosome targeted morpholine, the Aza-BODIPY and benzothiazole are connected through a-C = N-C-group, and the probe is a quinoxaline-derived Aza-BODIPY-AIE fluorescent probe. A precursor intermediate probe 1 is formed by connecting a fluorophore Aza-BODIPY and a rotor benzothiazole through a-C-C = N-group. The invention further discloses a synthesis method of the fluorescent probe and application of the fluorescent probe to lysosome viscosity detection. The probe system disclosed by the invention has significantly increased Stokes shift, and effectively avoids overlapping of excitation / emission spectrums; the fluorescent probe shows typical aggregation-induced emission (AIE) characteristics, and fluorescence enhancement is most remarkable under the condition that the water content is 40-50%; the fluorescent probe has wide-range viscosity response capability (2-610cP), 24 times of fluorescence enhancement can be generated at most, and the detection limit is as low as 0.27 cP; the lysosome co-localization performance is excellent, and the cell compatibility is good; the high-contrast real-time imaging monitoring on the viscosity of the living cell lysosome can be realized.

The present disclosure describes lysosome-targeting chimeras having at least one target-binding moiety capable of specifically binding a cell surface molecule or an extracellular molecule; and at least one thiol-responsive moiety. Methods of making and using the lysosome-targeting chimeras are also provided.

This invention discloses a method for preparing a lysosome-targeted polar fluorescent probe and its application in bioimaging, belonging to the field of chemical analysis and detection technology. The structure of the polar fluorescent probe is as follows: The lysosome-targeted polar fluorescent probe of this invention exhibits excellent polar sensing properties and significant aggregation-induced emission characteristics. With increasing solvent polarity, the fluorescence emission of the probe PHPT shows a significant redshift and a marked increase in fluorescence intensity. Within the polarizability range of 0.214–0.353, the maximum emission wavelength of the probe PHPT shows a good linear relationship with the solvent polarizability. The probe also exhibits good photostability. More importantly, the polarity detection properties of the probe PHPT are unaffected by pH and various small biological molecules. The probe PHPT has low cytotoxicity and is suitable for bioimaging. PHPT has the ability to precisely target lysosomes and can be used to detect decreased cell polarity and increased polarity during autophagy, and can be used to monitor physiological activities related to changes in intracellular polarity.

The present disclosure provides conjugates comprising a moiety targeting a lysosomal targeting molecule, a linker, and an antibody that specifically binds to a targeted degraded cell surface target molecule or extracellular target molecule.

The application discloses a kind of targeting lysosome polypeptide, lysosome fluorescent probe and kit, belong to the field of biotechnology.The targeting lysosome polypeptide sequentially includes A, B, C, D four parts from N-terminal to C-terminal, wherein, A part is cell penetrating peptide sequence, B part is lysosome targeting positioning sequence, C part is connecting peptide sequence, D part is fluorescent protein sequence.The polypeptide can quickly enter cell and target positioning in lysosome, has good biological safety and stability, can be applied as lysosome fluorescent probe, is suitable for the fluorescence imaging of lysosome in different living cells, and has specificity for lysosome staining.And lysosome polypeptide probe kit can be developed therefrom, to provide accurate lysosome organelle positioning and convenient application for scientific experimental research.

Provided herein are compositions, systems, kits, and methods for treating nervous system injuries caused by trauma or neurodegeneration or aging in a subject by administering a CSPG or SOCS3 reduction peptide (CRP and SRP respectively), or a nucleic acid sequence encoding the CRP or SRP, wherein both the CRP and SRP comprise a cell membrane penetrating domain, and a lysosome targeting domain, and the CRP further comprises a chondroitin sulfate proteoglycan (CSPG) binding domain, and the SRP further comprises a suppressor of cytokine signaling-3 (SOCS3) binding domain.

The application discloses a kind of lysosome-targeting protein modulators based on upconversion nanomaterial-DNA nanostructure and preparation method thereof.The lysosome-targeting protein modulators are combined by covalent bond from carboxyl functionalized upconversion nanoparticles and amino-modified DNA nanostructure, mainly enter cancer cells through folate receptor, after near infrared light illumination and glutathione response, the target protein combined is transported into lysosome and degraded.The lysosome-targeting protein modulators of the application have the advantages of light affinity, high controllability and storage stability, are easy to be metabolized by organism, and have good application prospect in the field of cell biology and cancer targeted therapy.

The present invention provides a glucose transporter (GLUT)-based lysosome targeting chimera. The lysosome targeting chimera can effectively enrich and degrade in lysosomes different types of target proteins on the cell surface and outside the cell. The present invention further provides an application of the lysosome targeting chimera, and an antibody-drug conjugate obtained by conjugating the lysosome targeting chimera with a cytotoxic drug.

The invention discloses a polypeptide targeting lysosome, a lysosome fluorescent probe and a kit, and belongs to the technical field of biology. The polypeptide of the targeted lysosome sequentially comprises a part A, a part B, a part C and a part D from the N end to the C end, the part A is a cell penetrating peptide sequence, the part B is a lysosome targeted positioning sequence, the part C is a connecting peptide sequence, and the part D is a fluorescent protein sequence. The polypeptide can rapidly enter cells and target and locate in lysosome, has good biological safety and stability, can be used as a lysosome fluorescent probe, is suitable for fluorescence imaging of lysosome in different living cells, and has specificity for lysosome staining. Therefore, a lysosome polypeptide probe kit can be developed, and accurate lysosome cell device positioning and convenient application are provided for scientific experimental research.

The application discloses a dual-response fluorescent probe and a preparation method and detection application thereof, and belongs to the technical field of fluorescent probes. The probe is prepared by condensation reaction of 4-methyl-7-hydroxy-8-aldehyde coumarin and 4-morpholine aniline, and can simultaneously and specifically respond to peroxynitrite and viscosity. ‑ The probe specifically reacts with ONOO to generate a concentration-dependent fluorescence enhancement, has high selectivity, fast response and good linearity, and the fluorescence is significantly enhanced with the increase of viscosity. The probe has lysosome targeting properties, and can realize real-time imaging and dynamic monitoring of endogenous and exogenous ONOO ‑ in living cells, and presents a high-contrast fluorescent signal in a non-alcoholic fatty liver model mouse liver tissue slice, so that ONOO ‑ overproduction and viscosity increase in a pathological state can be accurately identified.

The application belongs to the field of fluorescent probes, and relates to a lysosome-targeting fluorescent probe and a preparation method and application thereof. An intermediate is prepared by mixing an aldehyde compound, 5-amino fluorescein and 7-bromoheptanoic acid, and then performing a reaction; the intermediate is mixed with morpholine, and then a reaction is performed, so that the lysosome-targeting fluorescent probe is obtained. The application belongs to the construction of a complex molecular system with flexible and modular Ugi four-component reaction, adopts a one-pot method, and is synthesized by a framework template conjugation method, and the yield of the product is between 60% and 80%. The fluorescent probe prepared in the application can target lysosomes, and can be used as a lysosome-targeting imaging agent for living cancer cells. The fluorescent probe containing ferrocene prepared in the application can target lysosomes, and can be used as a lysosome-targeting imaging agent and a therapeutic agent for living cancer cells. The fluorescent probe containing ferrocene prepared in the application can effectively inhibit the growth of Hela and other cancer cells.

Provided herein is a bifunctional lysosomal targeted degradation agent comprising: a peptide ligand that binds to an RGD binding integrin as a shuttle molecule for lysosomal degradation; and a protein binding agent that binds to a membrane of interest or an extracellular protein. The bifunctional degradation agents are useful, for example, for selective targeted degradation of membranes and extracellular proteins through endosomal / lysosomal pathways. Also provided herein are compositions comprising the bifunctional degradation agents and methods of using the bifunctional degradation agents.

The present disclosure provides conjugates comprising a moiety that targets a lysosomal targeting molecule, a linker, and an antibody that specifically binds a cell surface target molecule or extracellular target molecule that is targeted for degradation.

The application belongs to the technical field of biotechnology, and particularly relates to a lysosome-targeting probe and a preparation method and application thereof. The structural formula of the lysosome-targeting probe is shown in formula (I). In formula (I), A is selected from an oxygen atom and a sulfur atom, R1 is selected from a hydrogen atom and an aromatic ring group, R2 is selected from a cyano group and a group shown in formula (II), R3 is selected from an aromatic ring group, and R4 is selected from a hydrogen atom and an alkyl group with a carbon atom number of 1-20. The compound of the application can specifically target lysosomes in tumor cells, emit bright fluorescence, and has a good fluorescence co-localization effect with lysosomes in tumor cells. The compound can be used for lysosome imaging, and the fluorescence intensity thereof is positively correlated with the viscosity of lysosomes in living cells such as tumor cells. The compound can be used for monitoring the viscosity change of lysosomes in living cells under various conditions. The compound can be used as a photosensitizer and a treatment sensitizer, specifically ablates tumors through photodynamic therapy (PDT), restores the sensitivity of tumor cells to radiotherapy and chemotherapy, and enhances the treatment effect of radiotherapy and chemotherapy.

The application discloses a fluorescent probe based on rhodamine modified nucleoside and a preparation method and application thereof, and a structure formula of the fluorescent probe is as follows: the fluorescent probe is a novel fluorescent probe based on rhodamine modified nucleoside, is composed of rhodamine hydrazine-short-chain alkyne-2-deoxy cytidine, and has the advantages of high fluorescence intensity, good biological compatibility, good strong acid resistance, high sensitivity and good chemical stability. 3+ The fluorescent probe can be widely applied in the fields of in vivo and in vitro Fe detection, real-time monitoring of pH dynamics, preparation of pH test paper, cell imaging, construction of lysosome-targeting functional probes, design of in vivo contrast agents, treatment and diagnosis of gastrointestinal diseases and screening of related treatment drugs, and has great practical application value.

The present application belongs to the technical field of pharmaceutical chemistry, and discloses a lysosome-targeting chimera, which is composed of an azidated mesoporous polydopamine nanoparticle carrier, an alkyne-lysosome-targeting receptor ligand and an alkyne-ALK5 inhibitor. The present application uses the mesoporous polydopamine with high biocompatibility as a carrier, constructs a safe and effective anti-oxidation nano platform, removes reactive oxygen species, reduces the oxidative stress level, and then reduces the secretion of TGF-beta by liver macrophages, simultaneously loads the ALK5 small molecule inhibitor, specifically recognizes and captures ALK5, realizes precise targeting by combining the modified M6P with the high expression CI-M6PR receptor on the surface of HSC, and provides a new technology and idea for clinically treating liver fibrosis.