79 results about "Small molecule ligand" patented technology

The invention discloses a small molecule ligand drug screening method and system based on affinity prediction, and belongs to the technical field of biological medicine. The invention aims to solve the technical problem of low drug screening precision caused by molecular expression limitation, geometric invariance deficiency and insufficient multi-modal information fusion when virtual drug screening is carried out by using protein-ligand affinity. Comprising the following steps: acquiring ligand and protein structure information, and preprocessing to obtain coordinates and a feature matrix of ligand / pocket / residue; performing comprehensive representation, multi-feature flow self-adaption, geometric algebraic multi-layer perception and feature alignment processing on the feature matrix to obtain corresponding feature space representation; performing cross attention fusion and multi-scale interactive learning processing on the feature space representation in sequence to obtain fusion features; inputting the fused features into a multi-scale interactive learning module, and outputting final features; and finally, predicting the binding affinity of the ligand and the protein according to the fusion characteristics to obtain a binding affinity value.

The invention belongs to the field of medical dressing materials, and particularly relates to a metal organic framework / hydrogel composite material and a method and application thereof. The hydrogel composite material contains hydrogel and a metal organic framework, and the hydrogel composite material has a hybrid structure formed by mutual intersection of the hydrogel and the metal organic framework. The preparation method of the hydrogel composite material comprises the following step: carrying out coordination reaction on a solution containing metal ions, small molecular ligands and hydrogel to obtain the hydrogel composite material. The hydrogel composite material has the flexibility of the hydrogel and the mechanical strength and long-acting antibacterial property of the metal organic framework, the hydrogel and the MOFs are compounded to organically combine a flexible material and a rigid material, the performance of the hydrogel and the performance of the MOFs are improved, and the application value of the hydrogel composite material in the medical field is expanded. In practical application, the hydrogel has the advantages of promoting wound healing, resisting bacteria and having biocompatibility.

The invention relates to a ternary platinum-based ordered alloy catalyst, a preparation method thereof and a fuel cell, and the preparation method comprises the following steps: ball-milling and uniformly mixing an organic small molecule ligand, a Pt precursor, an M1 precursor, an M2 precursor and a carbon carrier, and calcining to obtain the ternary platinum-based ordered alloy catalyst, the small organic molecule ligand comprises doping elements, and the doping elements comprise an N element and / or an S element; in the precursors of M1 and M2, M1 and M2 are each independently a transition metal element. According to the preparation method, ball milling and high-temperature calcination are combined, small organic molecule ligands are added in the ball milling and mixing stage to participate in the reaction, coordination bonds can be formed among the small organic molecule ligands, Pt particles and transition metal particles, S and / or N in the small organic molecule ligands are doped into a bulk phase of alloy particles, meanwhile, the phenomenon of catalyst agglomeration caused by ball milling can be effectively prevented, and the catalyst stability is improved. No solvent is needed in the preparation process, especially no organic solvent is used, and the preparation method is simple, safe and suitable for large-scale production.

The invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a method for separating active components in tobacco based on liquid-phase segmented separation, SPR, affinity chromatography enrichment and mass spectrometry detection, a product and application. According to the method, liquid chromatography separation, SPR detection screening, affinity chromatography enrichment and mass spectrum identification technologies are fused, and active small molecules are screened and enriched from a complex system by virtue of high sensitivity of SPR and accuracy of mass spectrum. The method comprises the following steps: firstly, carrying out liquid chromatography segmented separation on extract components to improve SPR detection precision and affinity enrichment efficiency; by means of specific binding of Ni Sepharose FF (NTA) resin and a His tag, more target proteins are fixed, and the micromolecule enrichment effect is further enhanced; and finally, identifying the molecular structure by using mass spectrum, and locking the bioactive small molecule combined with the target protein. According to the strategy, efficient enrichment of small molecule ligands is achieved, and a new way is provided for early-stage development of small molecules in drug discovery. 6.

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 discloses a Zn < 2 + >-lanthanide ion complex co-doped CIZS quantum dot and a method thereof. The method comprises the following steps: (1) preparing a multi-element sulfide quantum dot; (2) preparing a lanthanide ion complex; (3) preparing CIZS quantum dots coated with Zn < 2 + >; and (4) preparing the lanthanide ion complex doped CIZS (at) ZnS quantum dot. The luminescent property of the quantum dot is improved by utilizing rich f-f electron transition energy level of lanthanide elements and through additional absorbed light quantum energy transfer or through structure doping on the surface of the quantum dot. The key point is that the problem that the lanthanide ions (Ln < 3 + >) are difficult to dope the sulfenyl quantum dots is overcome in a breakthrough manner, so that the lanthanide ions (Ln < 3 + >) and the complex thereof are structurally doped and permeated to the CuInZnS quantum dots. The ZnS-coated lanthanide ion complex-doped CuInZnS quantum dot is prepared by the following steps of: performing Zn < 2 + > coating on the surface of the quantum dot under proper reaction conditions by selecting a combination of an organic small molecule ligand and lanthanide ions to form a lanthanide ion complex, and then introducing the lanthanide ion complex to obtain the ZnS-coated lanthanide ion complex-doped CuInZnS quantum dot.

This application discloses a phenanthroline benzimidazole-structured polyimide single rare-earth ion coordination full-spectrum luminescent material, its preparation method, and its applications, belonging to the field of polymer luminescent material preparation technology. This phenanthroline benzimidazole-structured polyimide single rare-earth ion coordination full-spectrum luminescent material comprises a phenanthroline benzimidazole-structured polyimide, a rare-earth ion, and a β-diketone-structured small organic molecule ligand bound through coordination. This polymer single rare-earth coordination material retains the advantages of polyimide while exhibiting the characteristics of rare-earth ions (Ln... 3+ The addition of ) brings special optical properties, coordination polymers and rare earth ions Tb 3+ PI-Tb formed after coordination 3+ It can emit full-spectrum white light (CIE = (0.31, 0.35)) and exhibits excellent thermal stability and solubility.

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.

The invention discloses a compound for targeted ubiquitination degradation of USP7 protein, and a medicinal composition and application thereof. The structural formula of the E3 ubiquitin ligase complex is as shown in formula I. A is a specific protein ligand in the E3 ubiquitin ligase complex; l is a bivalent linking group between a USP7 protein small molecule ligand and a specific protein ligand in an E3 ubiquitin ligase complex. The protein degradation chimera has the activity of inhibiting USP7 protein and the activity of degrading USP7 protein, and can effectively inhibit malignant proliferation of acute lymphatic leukemia cells, so that the protein degradation chimera can be used for related diseases with abnormal expression of USP7 protein.

The present application relates to methods of treating and imaging cancer. The methods involve providing a first agent comprising a first targeting component coupled to a cancer therapeutic component or an imaging component and providing a second agent comprising a second targeting component alone, wherein the second targeting component increases the uptake, internalization, and / or retention of the first targeting component coupled to a cancer therapeutic component or imaging component. The first and second agents are then administered to a subject having cancer to treat cancer. Also disclosed is a combination therapeutic or a combination imaging system, each comprising the first and second agents.

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 application provides a method for preparing 7-octene-1-ol polyoxyethylene ether and application thereof, and the method comprises the following steps: S1: adding sodium metal into 7-octene-1-ol to obtain a precursor solution; S2: adding a small molecule ligand into the precursor solution and then introducing ethylene oxide to obtain an oligomer intermediate; wherein the small molecule ligand comprises at least one of a β-diketone compound and an imidazole compound; S3: continuously introducing ethylene oxide into the oligomer intermediate to obtain 7-octene-1-ol polyoxyethylene ether. The method can effectively improve the double bond retention rate of 7-octene-1-ol polyoxyethylene ether, reduce the risk of side reactions such as addition, rupture or isomerization of unsaturated structures in the polymerization process, and improve the reaction efficiency and structural integrity of the target product in the subsequent copolymerization reaction.

The invention relates to the field of biological materials, and provides an injectable hydrogel pre-gelatinizing solution based on ligand regulation and control and a preparation method and application of the injectable hydrogel pre-gelatinizing solution. A multivalent metal ion; a small molecule ligand; wherein the alginic acid compound comprises alginic acid or alginate and a derivative thereof; the molar ratio of the micromolecule ligand to the multivalent metal ions is marked as L / M; defining the minimum L / M for keeping the system in a sol state at the set temperature and ion strength as a critical ligand ratio, and recording the critical ligand ratio as CLR; in the pre-gelatinizing solution, L / M is greater than or equal to CLR. The pre-gelatinizing solution can be smoothly injected through a fine needle, can quickly form a gel shell at an interface to prevent leakage after being injected to a water-containing environment, has continuous self-enhancement performance, and is wide in application range.

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.

The present invention discloses a method for predicting drug-target affinity based on multi-shell and extended connectivity fingerprints, using protein-ligand complexes in the PDBbind database as a data set; modeling the binding pockets of macromolecular proteins and small molecule ligands, constructing N shells outward from the geometric center of the ligand, and mapping protein atoms to each shell according to the spatial coordinates of the protein atoms; classifying ligand atoms into multiple categories through features such as atomic symbols, explicit valences, etc.; taking all specific atom pairs as the features of this shell, and superimposing the features of multiple shells to obtain the feature vector of the complex; through 3D slicing of the complex features, using Transformer to learn the shell atom pair features. The present invention solves the problem that existing methods cannot characterize long-range interactions; through 3D slicing of the complex features, Transformer can well learn the shell atom pair features, thereby changing the performance of the characterization.

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 present invention belongs to the field of biomedicine technology and specifically relates to a small molecule ligand-rucaparib conjugate and a preparation method thereof. The small molecule ligand-rucaparib conjugate is a combination of one or both of a biotin-rucaparib conjugate and a lactobionic acid-rucaparib conjugate. Rucaparib is coupled to the small molecule ligand through an amidation reaction, thereby improving rucaparib's tumor targeting ability and thereby enhancing its inhibitory effect on tumor cells. In particular, the dual-targeting effect of biotin / lactobionic acid-rucaparib composite nanoparticles, which are self-assembled from the small molecule ligand complex, is more significantly inhibited against double-positive tumor cells such as biotin receptors and asialoglycoprotein receptors. Furthermore, the biotin / lactobionic acid-rucaparib composite nanoparticles have a significant application prospect due to their safety advantage over normal cells.

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.

The application discloses a lead sulfide quantum dot photoelectric device and a preparation method thereof. The hole transport layer of the photoelectric device is a three-layer structure, a lower interface modification layer is a lead sulfide quantum dot film of a thiol small molecule ligand formed on a lower surface of a P-type organic polymer layer, and an upper interface modification layer is a three five-fluorophenyl boron doped poly[bis(4-phenyl)(2,4,6-trimethylphenyl) amine] film formed on an upper surface of the P-type organic polymer layer. The application forms a stable ohmic contact between a plurality of P-type polymer hole transport layers and a gold electrode by using the thiol small molecule modified PbS quantum dot transition organic / inorganic interface and the three five-fluorophenyl boron doped poly[bis(4-phenyl)(2,4,6-trimethylphenyl) amine] as a universal material for eliminating the barrier with the gold electrode, effectively blocks water and oxygen in the air from corroding the lead sulfide quantum dots, and significantly improves the efficiency and working stability of the lead sulfide quantum dot photoelectric device.

The application belongs to the technical field of pharmaceutical chemistry, and particularly relates to a compound capable of combining with cell division cycle 20 (Cdc20) and a composition thereof, and particularly discloses a compound capable of combining with cell division cycle 20 (Cdc20), wherein the compound is shown as (I); the compound can further become a targeted protein degradation agent and a pharmaceutical composition, and is used for treating or preventing diseases caused by promoting abnormal cell division after Cdc20 activates an APC complex, and the compound has high Cdc20 combining ability.

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.

A compound for degrading USP7 protein by means of targeted ubiquitination, a pharmaceutical composition thereof and the use thereof. The structural formula thereof is shown as formula (I), wherein A is a specific protein ligand in an E3 ubiquitin ligase complex, and L is a divalent linker group between a small molecule ligand of the USP7 protein and the specific protein ligand in the E3 ubiquitin ligase complex. The protein degradation chimera has both USP7 protein inhibitory activity and USP7 protein-degrading activity, can effectively inhibit malignant proliferation of acute lymphoblastic leukemia cells, and thus can be used for diseases associated with abnormal USP7 protein expression.

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.