38 results about "Small molecule ligand" patented technology

The invention discloses application of Kitl in promoting meiosis of germ cells cultured in vitro. By adding a small molecule Kit ligand (Kitl), germ cells (including primordial germ cells PGCs, primordial germ cell-like cells PGCLCs and the like) cultured in vitro are promoted to enter and complete the first meiosis earlier stage, meiosis key protein expression is improved, and homologous chromosome association and recombination efficiency is improved. The method has a wide transformation medical prospect in the fields of human assisted reproductive technology and reproductive medicine.

The invention relates to a preparation method of a highly ordered, soft and malleable MXene-based organic-inorganic hybrid superlattice material, which comprises the following steps: carrying out surface modification on hydrochloric acid acidified Ti3C2Tx nanosheet aqueous dispersion by using oleylamine, washing the product with ethanol, drying, and dispersing in trichloromethane; and adding small molecular ligands such as oleic acid into the dispersion liquid, and then carrying out solvent evaporation assembly to obtain the superlattice material with a long-range ordered layered structure. The film shows intrinsic flexibility and can be directly formed into a macroscopic three-dimensional block through physical folding and mold pressing. The mechanical property of the MXene material is fundamentally regulated and controlled through molecular intercalation and ordered assembly, integrated construction from a nanoscale ordered structure to a macroscopic functional material is achieved, and the obtained MXene-based organic-inorganic hybrid superlattice material has electrical conductivity, structural orderliness and good deformability; the method has important application prospects in the fields of flexible electronic devices, deformable electrodes, intelligent sensing and the like.

The invention discloses a small molecule binding protein design method. The method comprises the following steps: S1, a structure acquisition step: acquiring a compound structure of a target small molecule ligand and protein; s2, a candidate sequence generation step: generating a candidate protein sequence set by adopting a protein generation model and adjusting parameters corresponding to the protein generation model according to the compound structure in the step S1; s3, a primary screening step; compounding the candidate protein sequence set in the step S2 with the small molecule ligand in the step S1, predicting a compound structure I, and screening a potential sequence from the compound structure I; s4, a fine screening stage: compounding the potential sequence screened in the step S3 with the small molecule ligand in the step S1, predicting a compound structure II, and screening a preferred protein sequence I from the compound structure II. Through deep fusion of AI generation and physical screening, a layer-by-layer progressive accurate screening funnel is constructed, and the false positive rate is greatly reduced.

This invention discloses a ligand-free electrodeposition method for growing platinum nanowire arrays on a substrate, with lengths reaching up to approximately 10 μm. The method exhibits a wide deposition potential range of -0.5 V to -7 V. By adjusting the deposition time, the length of the platinum nanowires can be controlled on the substrate without a template or small molecule ligands. Furthermore, the density of the platinum nanowires can be controlled by varying the concentration of the silane coupling agent. Moreover, this synthesis can be extended to conductive substrates, allowing the platinum nanowire arrays to be directly used as working electrodes, providing significant application potential in fields such as electrocatalysis. This invention offers advantages such as simple process, mild reaction conditions, low cost, and the precise controllability, ease of operation, and environmental friendliness of electrodeposition for synthesizing nanomaterials.

The invention discloses a mixed ligand modified cesium lead halide perovskite nanocrystal and a preparation method thereof, and the preparation method comprises the following steps: (1) adding CsBr and PbBr2 in an equal molar ratio into a P-AMDL polymer solution to obtain a CsPbBr3 precursor solution; (2) injecting the precursor solution into a toluene solvent, and then settling and purifying by using an n-hexane solvent to obtain a P-AMDL modified CsPbBr3 solution; (3) introducing an oleic acid oleylamine ligand to obtain CsPbBr3 modified by a mixed ligand; and (4) optimizing an ion exchange method by combining a mixed ligand strategy to obtain the mixed ligand modified CsPbBrxI3-x. According to the invention, the problem of wide particle size distribution of nanocrystals synthesized by an LARP method at room temperature is solved, and the all-inorganic cesium-lead halide perovskite nanocrystals with fewer defects, more regular morphology and better ultraviolet stability are successfully prepared. The'micromolecule + polymer 'mixed ligand strategy gives consideration to the regulation and control precision of the micromolecule ligand and the stability of the polymer ligand, and is an effective means for optimizing the morphology and performance of the perovskite nanocrystal.

Disclosed herein is a small molecule targeted drug conjugate for anti-influenza chemotherapy and immunotherapy. The disclosed drug conjugate may form an adaptor to recruit additional CAR T cells or other immune cells for precise elimination of influenza virus-infected cells in a subject. Concurrently administered antibodies or pre-existing immunity in influenza-virus infected subject works well with the targeted conjugate to eliminate virus infected cells, saving valuable time for rescuing late stage patients.

This invention belongs to the field of pharmaceutical chemistry technology, and discloses a compound and its uses. Specifically, it relates to a CRBN small molecule ligand compound based on a pyridazine-glutarimide core skeleton (PDG), its composition, and its application. It also relates to a protein degrading agent based on a CRBN small molecule ligand compound based on a pyridazine-glutarimide core skeleton (PDG) and its application. Specifically, the CRBN small molecule ligand compound is shown in (Ⅰ): wherein R... 1 and R 2 Selected from one or more of the following: fused rings attached to a pyridazine core, H, alkyl, OR, F, CN, CF3, NR2, Ph, 4-Py; Y selected from one or more of CH, CD, CF, and N; R 3 Selected from one or more of OR, NR2, CHR2, and C≡CR; R 4 Selected from H or alkyl.

A PAMAM-based protein degradation system and a method of preparation and use thereof are provided. The protein degradation system comprises: a silica nanoparticle core; and a poly(amidoamine) dendrimer (PAMAM) layer coated on a surface of the silica nanoparticle, wherein the PAMAM layer is linked via amide bonds to three small-molecule ligands: MDM2 protein ligand Idasanutlin, GLUT1 protein ligand Lavendustin B and E3 ubiquitin ligase ligand Thalidomide-NH—CH2—COOH. The nanoparticle protein degradation system cooperatively degrades MDM2 protein and GLUT1 protein. This cooperative degradation strategy not only effectively suppresses proliferation and energy metabolism of tumor cells, but also significantly enhances the stability of p53 protein. By restoring the normal function of p53 protein, tumor cell growth is further inhibited, providing a new strategy for cancer therapy.

The application discloses a preparation method of fluorine-containing Fe3O4 nano-assemblies and application of the fluorine-containing Fe3O4 nano-assemblies in intracellular protein delivery, and the preparation method comprises the following steps: preparing Fe3O4 nanoparticles and small-molecule ligands containing fluorine alkyl chains respectively, and the two are combined through ligand exchange reaction to form fluorine-containing Fe3O4 nanoparticles; the fluorine-containing Fe3O4 nanoparticles can be self-assembled with proteins to form stable complexes through the hydrophobic effect and electrostatic effect of the fluorine alkyl chains. The fluorine-containing Fe3O4 assemblies provided by the application have universality as intracellular protein delivery carriers, can effectively deliver proteins with different isoelectric points and molecular weights to tumor cells, do not affect the biological activity of the cargo proteins, have small toxicity to cells, and have good biocompatibility. The protein delivery efficiency of the assemblies is further improved under the guidance of an external magnetic field, so that the killing effect of therapeutic proteins on tumor cells is enhanced, and the assemblies have application potential in the field of tumor treatment.

The application provides a modular assembly technology of a cell penetrating peptide-mediated polypeptide or microprotein targeting chimeric compound and application thereof, and the targeting chimeric compound comprises at least one penetrating peptide module, at least one targeting polypeptide module and at least one small molecule ligand module which are connected with each other, and the targeting polypeptide module is a polypeptide sequence capable of being combined with a target protein. The application has the characteristics and advantages that the cell penetrating peptide-mediated polypeptide or microprotein modular assembly targeting chimeric compound provided by the application adopts modular design, and each sequence or small molecule compound module with different functions can be replaced and superimposed according to needs, and all polypeptide module parts can be circularized or modified with a secondary microprotein structure. The design idea greatly enhances the use effect and application range of the targeting drug.

The invention discloses a device for detecting human blood protein binding activity and a detection method, and aims to solve the problems that the existing equilibrium dialysis method is too long in time consumption and tedious in operation. The device comprises a pressure dialysis tube assembly, a pressure control module and a temperature control module. The pressure dialysis tube assembly is provided with a dialysis membrane which can intercept human serum albumin in a sample chamber and allow free small molecule ligands to pass through. The pressure difference between the pressure air inlet and the pressure balance port is accurately adjusted through the pressure control module, zero pressure difference can be kept in the combination stage to prevent leakage, positive pressure is applied in the dialysis stage to drive free ligands to quickly pass through a dialysis membrane, and the separation time is greatly shortened. The temperature control module ensures that the whole process is in a constant-temperature environment, and physiological correlation and repeatability of data are ensured. The detection method comprises the steps of sample mixing, constant-temperature combination, pressure dialysis, dialysate collection, ultraviolet spectrophotometry determination and the like. According to the invention, rapid, accurate and high-throughput detection of the binding activity is realized.

The application discloses a kind of lead sulfide quantum dots with adjustable light absorption range, preparation method and application thereof.Sulfur source is dissolved in short-chain amine solvent, lead source and organic small molecule ligand solution dissolved in organic polar solvent are added, and then sulfur source solution is added, and the reaction is stirred at a temperature of 0-100 DEG C to obtain a reaction product;anti-solvent is added, and the product is washed and dried to obtain lead sulfide quantum dots with uniform particle size and adjustable light absorption range.By adjusting the content of precursor, reaction solvent and temperature, and under the action of n-butylamine, PbS quantum dots with adjustable light absorption range are directly synthesized in one step, which solves the limitations of small light absorption range and low yield of quantum dot ink direct synthesis, and obtains quantum dots with a light absorption range of 1000nm-2000nm wavelength.The synthesized quantum dots have achieved preliminary application in photoelectric detector.

Small molecule AhR ligands are disclosed. The ligands can induce the differentiation of Tr1 cells to suppress pathogenic immune responses without inducing nonspecific immune suppression. Methods of treatment of autoimmune diseases using the AhR ligands are also disclosed.

This invention discloses a radiotracer targeting pan-KRAS mutant proteins, its preparation method, and its applications. The tracer uses small molecule ligands that specifically recognize multiple KRAS mutant proteins as targeting modules, and is coupled to diagnostic radionuclides through an optimized linkage system. This tracer is independent of specific mutation sites and can broadly and specifically bind to multiple high-frequency KRAS mutant subtypes, including G12C, G12D, and G12V. Based on PET / SPECT imaging, this tracer enables rapid, non-invasive, systemic, visualized, and quantitative assessment of KRAS mutant protein expression load in living tumors, overcoming the invasiveness, spatiotemporal limitations, and tumor heterogeneity challenges of traditional biopsies. It provides a novel molecular imaging tool for accurate companion diagnosis of KRAS-mutant tumors, screening of patients benefiting from pan-KRAS inhibitors, and monitoring efficacy, possessing significant clinical translational value.

The present invention pertains to the field of targeted protein degradation (TPD) and target protein recruitment (TPR) providing a versatile platform for TPD, TPR and other applications dependent on cell surface ternary complex formation. In particular, the present invention provides a compound comprising a macromolecular hydrophilic polymer scaffold which is conjugated with several copies of at least two different protein binding ligands. The polymeric scaffold of the invention enables the use of small molecule ligands for target proteins of interest. Furthermore, the invention also relates to a composition comprising said polymeric scaffolds and uses thereof, e.g. for inhibiting or removing malignant or unwanted proteins; or for use in the targeted recruitment of effector cells such as CAR-T cells.

The present disclosure relates to riboswitches and polynucleotide cassettes that modulate the expression of chimeric antigen receptors (CARs) in response to small molecule ligands, wherein the polynucleotide cassettes comprise the riboswitches and aptamers disclosed herein. Also provided are methods for generating a population of T cells wherein the T cells comprise a CAR transgene comprising an expression construct that inductively expresses a CAR in response to a small molecule inducer that binds to a riboswitch aptamer, which is part of the expression construct. Also provided are methods for treating cancer by administering to a patient in need thereof: (i) a population of T cells comprising an induced CAR comprising the riboswitch described herein; and (ii) a small molecule inducer (aptamer ligand) disclosed herein.

The present application relates to the technical field of biological medicine, and specifically discloses a small-molecule coupling compound targeting ASGPR, which has the following general formula: wherein X is a small-molecule ligand with the ability to target ASGPR; and Y is a derivative of cucurbitacin B. . The small-molecule coupling compound can be used in the preparation of a drug targeting ASGPR and having the functions of precise chemotherapy and radiotherapy sensitization. The small-molecule coupling compound prepared by the present application can achieve precise killing of liver cancer cells; the water solubility of cucurbitacin B is improved after coupling; the small-molecule coupling compound integrates precise chemotherapy and radiotherapy sensitization, and can significantly enhance the cancer-killing effect in combination with low-dose radiotherapy; and the small-molecule coupling compound has no obvious systemic toxicity and is well tolerated by patients.

This disclosure provides a small molecule of formula (I) that binds to an aptamer. Also intended are riboswitches and polynucleotide cassettes for regulating the expression of a target gene in response to the small molecule, the polynucleotide cassette comprising the aptamer disclosed herein. The small molecule disclosed herein, bound to the aptamer disclosed herein, is a modulator of target gene expression, and the target gene comprises a riboswitch containing the aptamer described herein. JPEG2026524820000284.jpg40164

The invention relates to a reaction plate for high-throughput screening of low-adsorption nuclear drugs as well as a preparation method and application of the reaction plate, and belongs to the technical field of biological medicines. The reaction plate comprises a substrate with a plurality of micropores in the surface and a coating formed on the inner surfaces of the micropores, the inner surfaces of the micropores are connected with the coating through covalent bonds; the coating is a hydrophilic-hydrophobic binary synergistic patterned coating; a hydrophilic area of the coating is a polyethylene glycol silane layer, and a hydrophobic area of the coating is a fluorocarbon polymer layer. According to the reaction plate disclosed by the invention, through special surface chemical treatment, the non-specific adsorption of ultralow-concentration (picomole to nanomole level) nuclear drug molecules (especially peptides, oligonucleotides and small molecule ligands) on the surface of a container can be remarkably reduced; the key technical problems of signal loss, inaccurate detection, non-repetitive results and the like caused by adsorption in the high-throughput screening process are effectively solved. The invention further provides a preparation method of the reaction plate, and the preparation method is stable in process and suitable for large-scale production.

The invention provides a kit for detecting tumor cells based on electrochemical analysis and application of the kit, and belongs to the technical field of biosensing. The invention discloses a kit for detecting tumor cells based on electrochemical analysis. The kit comprises an ordered functionalized electrode, a recognition catalytic probe, heme, tyramine alkyne, hydrogen peroxide, a double-chain signal probe modified with an azide group and an electrochemical active group, and a solution containing cuprous ions. According to the kit, a double-target collaborative tumor cell recognition strategy combining a small molecule ligand and a nucleic acid aptamer is adopted, so that the selectivity and the detection specificity of target tumor cells are remarkably improved; by virtue of an ordered functionalized electrode interface, the capture efficiency of target tumor cells is effectively improved, and the interface adsorption of non-target components is reduced; in addition, through the synergistic signal amplification effect of proximity oxidation labeling and click chemistry, background interference caused by non-target cells is effectively inhibited while high-sensitivity detection is achieved, and the probe still has excellent detection performance in complex biological samples.

The present invention generally relates to recombinant receptor polypeptides and recombinant receptors, and cells expressing thereof, capable of activating cellular cytokine pathways by complexing small molecule ligands. The invention also relates to nucleic acid molecules encoding the recombinant cytokine receptors of the present invention.

The present application belongs to the field of synthetic biology, and relates to a kind of unstable domain mutant based on prokaryotic transcription factor TtgR and its application.The present application constructs protein level reversible control switch by directional modification of prokaryotic transcription factor, and upgrades traditional transcription level regulation to protein level precise regulation.The regulation system (TtgR regulation system) has modular structure and wide adaptability: in specific embodiments, the coding sequence of reporter gene EGFP has been connected and modified into a fusion protein, and can precisely regulate the expression of EGFP under the induction of various small molecule ligands.The system can be applied to the operable connection of the coding sequences of various target proteins, including but not limited to CAR-T, CAR-NK related functional proteins, IL-2 and other cytokines, and other therapeutic proteins, functional proteins, etc.

This invention discloses a method for site-specific fluorescent labeling of proteins in cell lysates and its applications, belonging to the field of pharmaceutical bioengineering technology. Utilizing genetic code amplification technology, non-natural amino acids containing azide groups are introduced at specific sites of the target protein. A long-lifetime terbium complex modified with dibenzocyclooctylene is directly added to the cell lysate, enabling copper-free click chemistry labeling of the target protein. This method exhibits good biocompatibility and wide applicability, and can construct CoraFluor-DBCO-labeled protein target libraries. Furthermore, a time-resolved fluorescence resonance energy transfer (TR-FRET) screening system is constructed, utilizing the long fluorescence lifetime of the terbium complex to filter out biological background fluorescence and improve the signal-to-noise ratio. Competitive TR-FRET enables homogeneous screening of small molecule ligands targeting the target protein in the lysate. This method avoids protein purification steps, is simple to operate, and has high screening efficiency.

This invention discloses a PARG small molecule degrader, its preparation method, and its applications. In this application, an analogue of the PARG small molecule ligand JA2131 is structurally modified by linking the nitrogen atom on the rigid piperazine ring to an E3 ligase ligand, yielding the proteolytic targeted chimeric (PROTAC) molecule PargGone. Experimental verification shows that the compound PargGone is a novel PARG small molecule degrader and possesses the ability to kill gastric cancer cells, making it suitable for use as a drug for the broad treatment of cancer diseases.

The present application relates to a PROTAC targeting a Bcl-xL protein and a use thereof. Specifically, the present invention provides a compound of formula I or a pharmaceutically acceptable salt, ester, prodrug, solvate, stereoisomer or deuterated compound thereof: A-L-E (I), wherein A is a small molecule ligand moiety targeting a Bcl-xL protein; E is a small molecule ligand moiety targeting an E3 ubiquitin ligase complex; and L is a linker. The compound or composition of the present invention can be used for selectively killing one or more senescent cells or treating senescence-related diseases or disorders in a subject.

The invention belongs to the technical field of fluorescent nano-materials, and particularly relates to a rare earth doped inorganic nano-luminescent material co-coordinated by a micromolecule ligand and an organic dye. According to the invention, the micromolecular ligand and the organic dye are competitively coordinated on the surfaces of the rare earth doped inorganic nanoparticles together, and the micromolecular ligand is used as a physical isolation and singlet oxygen quencher, so that the luminous intensity of the organic dye sensitized rare earth ions can be further enhanced, and the organic dye has the capabilities of inhibiting aggregation quenching and resisting photobleaching; and the overall stability of the sensitization system is improved. The invention provides a new technical path for optimizing dye-sensitized rare earth luminescence, is expected to be used as a new-generation super-resolution imaging probe, and shows huge application potential in advanced fields of deep tissue biomedical research, high-precision disease diagnosis, drug research and development and the like.

This invention relates to the field of pharmaceutical technology, specifically disclosing an etodoxa acid small molecule hydrogel and its preparation method. The hydrogel is prepared by mixing etodoxa acid with three small molecule ligands (glucamine, arginine, and lysine). The morphological characteristics, thermodynamic properties, intermolecular interactions, and dissolution effects of the hydrogel were verified using SEM, rheological testing, DSC, XRPD, FTIR, and dissolution experiments. The preparation method is simple, involving mixing etodoxa acid with the small molecule ligands, adding a small amount of deionized water, and shaking. The resulting hydrogel significantly improves the solubility and dissolution / release rate of etodoxa acid. Compared to etodoxa acid crystals, the hydrogel exhibits significantly better solubility, dissolution / release rate in water than individual crystalline drugs or their physical mixtures, demonstrating the potential to improve the bioavailability of etodoxa acid. This provides a new formulation strategy for addressing the solubility defects of poorly soluble drugs and for combination drug use.

The present disclosure provides small molecules of formula (I) that bind to aptamers. Also contemplated are riboswitches and polynucleotide cassettes that modulate the expression of a target gene in response to the small molecules, wherein the polynucleotide cassettes comprise the aptamers disclosed herein. The small molecules disclosed herein bound to the aptamers disclosed herein are modulators of expression of a target gene, wherein the target gene contains a riboswitch comprising the aptamers described herein.

This invention provides a FAP-targeted engineered exosome for treating hypertrophic scars, its preparation method, and its application, belonging to the field of biopharmaceutical manufacturing technology. After co-incubation with an ferroptosis inducer, the FAP-targeting small molecule ligand SUC-Lys(Ac)-PEG3-UAMC1110 is covalently linked to the exosome membrane surface using an EDC / NH-mediated amide bond coupling strategy to obtain engineered exosomes. These engineered exosomes are then used to prepare microneedle patches. The microneedle patches allow the engineered exosomes to accumulate at the scar site and preferentially enter FAP-highly expressed scar fibroblasts, inhibiting their abnormal proliferation, migration, and pro-fibrotic phenotype, reducing collagen deposition, and promoting hypertrophic scar tissue remodeling. This invention combines the advantages of strong targeting, low off-target toxicity, minimally invasive drug delivery, sustained local retention, and stable efficacy, making it suitable for preparing drugs to treat or improve hypertrophic scars, and possessing good clinical translational potential.

The invention discloses a PROTAC medicine for targeted degradation of ACLY protein and a preparation method and application of the PROTAC medicine, and belongs to the technical field of medicine. The structure of the PROTAC drug for targeted degradation of the ACLY protein is shown as a general formula A-L-B, A is an ACLY protein ligand NDI-091143 or a derivative thereof, L is a connecting chain, and B is a small molecule ligand of E3 ubiquitin ligase protein; the connecting chain is connected with A and B through covalent bonds; the micromolecular ligand of the E3 ubiquitin ligase protein is at least one of pomalidomide, thalidomide, lenalidomide or a derivative thereof; the PROTAC drug for targeted degradation of the ACLY protein is applied to preparation of an ACLY protein degradation agent and preparation of drugs for prevention and / or treatment of MAFLD, obesity or diabetes mellitus.