149 results about "Small molecule ligand" patented technology

The invention discloses a construction and prediction method of an integrated drug target prediction system. The method comprises the following steps of: analyzing a protein crystal structure database; selecting the protein bound with the drug-like ligand small molecule or the protein with the small molecule ligand binding potential as a target point, and building a crystal structure database of targets; for these targets, collecting the information of the targets related to diseases, the biology type and the active small molecule ligand information, and integrating a comprehensive target screening database composed of an active site database, a pharmacophore database, a small molecular compound database and a target basic information database. Based on the comprehensive target screening database, the construction of the integrated drug target prediction system is realized through a script program or a PipelinePilot flow, and the probability of target prediction accuracy of the method is provided. The method provided by the invention exerts the three above technical advantages to provide the probability of target prediction, thereby providing effective basis for further experimental verification.

A system for electrostatically coating particles is provided. The system is particularly well suited for coating charged drug delivery particles (e.g., nanoparticles, microparticles) with a coating of opposite charge. The coating may include a targeting moiety such as a small molecule ligand, peptide, protein, aptamer, etc. The coated particles are biodegradable and/or biocompatible, have a near neutral zeta (ξ) potential, and are stable in serum. The invention also provides pharmaceutical compositions and kits including the inventive coated particles. Methods of preparing and using the inventive particles are also included.

The present invention describes small molecule ligand-drug conjugates and methods of using the small molecule ligand-drug conjugates for targeted treatment of cancer in a patient in need thereof. Further described are methods of sterilizing circulating tumor cells and determining drug concentration in cancer tissue.

The invention relates to a virtual screening method for a novel cancer-preventing or anti-cancer medicament by taking Keap1 as a target point. The method comprises the following steps of: 1) determining a PDB structural data of a Keap1 protein structure; 2) determining an active center according to an active cysteine residue site of the Keap1 by adopting molecular docking software, and setting active bags; 3) screening small molecule ligand; 4) establishing a small molecule ligand database for docking; 5) docking the small molecule ligand in the small molecule ligand database for docking and the active bags one to one according to the set active bags by using the molecular docking software; and 6) primarily determining a pilot medicament with chemical cancer-preventing or anti-cancer effect according to the sequencing of the docking results. The method can obtain a clue of an active compound in short time, and then screens the cancer-preventing or anti-cancer medicament by using animal horizontal screening or high-pass molecule platform screening so as to greatly improve the speed and the efficiency and shorten the research period of a new medicament.

The invention features a method of attaching a ligand that has a free carboxyl group to a solid support by adding an amino group to the ligand to form a ligand-amino derivative, converting the ligand amino derivative to a ligand sulfhydryl derivative, attaching the ligand sulfhydryl derivative to a protein to form a ligand-linker-protein conjugate, and applying the ligand-linker-protein conjugate to the solid support. The method is particularly useful for immobilizing small molecule ligands having a free carboxyl group, such as cloxicillin, to a lateral-flow test strip, in order to make a detection zone on the test strip that exhibits a clear signal and enhanced sensitivity.

The invention belongs to the field of rare earth-macromolecule complex luminescent materials, and particularly relates to a bonding type polymer-rare earth ternary complex luminescent material and a preparation method thereof. The bonding type polymer-rare earth ternary complex luminescent material is prepared by coordinating rare earth ions with polymer of bonded naphthoic acid ligand serving as a macromolecule ligand and any one of naphthoic acid, phenanthroline, and 2,2'-diphridyl serving as a micromolecule ligand. Not only is the method easily realized, but also the performances of the material prepared can be greatly improved, the problems in the prior art that the rare earth complex are uneven to disperse, poor in performances of polymer matrix and the like can be solved, and the bonding type polymer-rare earth ternary complex luminescent material and the preparation method thereof can develop a new way for preparing novel rare earth-macromolecule complex luminescent materials.

The invention is related to medicine, in particular, to oncology and immunology. The novel compounds of the general formula 1 or 2, exhibiting affinity for CD16a receptor have been proposed. There were also proposed novel modified proteins active towards CD16a receptor, selected from antibody or autogen conjugated by a modifying compound selected from compound of the general formula 1 or 2, which stimulate and direct antibody-dependent cellular cytotoxicity. The novel modified proteins (conjugates) could be used for destruction of definite targeted group of cells in organism, for example, cancerous cells or autoimmune lymphocytes. There were also proposed methods for conjugate preparation, pharmaceutical composition, and medicament, comprising modified proteins for treating oncology and autoimmune diseases.

The invention relates to a preparation method of a nucleotide-rare earth coordination polymer light-emitting material. According to the method, a hydrophilic light-emitting rare earth coordination polymer material is prepared from biomolecules including nucleotide, rare earth ions and micromolecule ligands through molecular self-assembling. According to the preparation method, because biomolecules are used as components, the prepared nucleotide-rare earth coordination polymer light-emitting material not only has a high light-emitting intensity, but also has good biocompatibility and hydrophily; through adoption of molecular self-assembling for preparation, the reaction is performed at room temperature and the conditions of a high temperature and a long reaction time, required by usual preparation, are not needed; therefore, the method is simple and easy to operate. The prepared light-emitting material has a good application prospect on the aspects of molecular sensing, tracer imaging, drug delivery, and the like.

The invention discloses a method for preparing binary perylene diimide derivative efficiently. The structural general formula of a compound is shown in the formula I. The preparation method comprises the following steps of: in inert atmosphere, carrying out reaction on the compound shown by a formula II, a copper catalyst, organic small molecule ligand and an organic base so as to obtain the compound shown in the formula I. The method has the advantages of being simple and efficient, light in environment contamination, cheap in raw material price, low in synthesis cost, good in universality and repeatability and the like, and can be promoted and used for synthesis of various other N substituent group binary perylene diimide derivative.

The invention relates to a computing method for processing interaction between small molecules and proteins. The method includes the following steps that (1) ligand file data of the proteins and the small molecules are read in; (2) atom types in ligands of the proteins and the small molecules are judged; (3) positions and angles of the ligands of the small molecules are randomly initialized; (4) a search protein algorithm is operated, coordinates and angles of the ligands of the small molecules are optimized, and a chemscore formula serves as an evaluation function; (5) the computing is ended after maximum iterative times are achieved; and (6) results such as root mean square deviation (RMSD), binding free energy delta G and coordinates of a binding site are analyzed and output. Compared with computing methods for processing the interaction between the small molecules and the proteins in prior art, the computing method for processing the interaction between the small molecules and the proteins has the advantages that when pollutants and biomacromolecules are interacted can be rapidly determined, and the like.

The invention relates to a macromolecular supported ternary amino acid Schiff base metallic copper complex catalyst formed by coordination of a macromolecular supported amino acid Schiff base metallic complex and micromolecular ligand. By utilization of the catalyst for catalytic oxidation of ethyl benzene and isopropyl benzene under normal pressure and at a temperature of between 105 and 115 DEG C, the conversion rate of the ethyl benzene is 20 percent, the selectivity of an acetophenone product is 100 percent, and no byproducts are generated; and although the conversation rate of the isopropyl benzene is 25 percent, the selectivity of a product, namely 2-phenyl-2-propyl alcohol (PP) is 100 percent. The catalyst has high activity and selectivity, and simultaneously has the following advantages in an oxidation system: firstly, the catalyst can be separated from a reactant and products through filtration; secondly, an oxidant, namely oxygen, does not pollute the environment; and thirdly, the system does not use any additive.

The invention discloses a method used for increasing the stability of a water phase quantum dot. According to the method, an ionic liquid and the water phase quantum dot are subjected to ligand exchange so as to obtain a modified quantum dot ionic liquid, wherein the boiling point of the obtained modified quantum dot ionic liquid is high, is usually higher than 200 DEG C, and the stability of the modified quantum dot ionic liquid is always better than that of small molecular ligands, such as mercaptoacetic acid, mercaptopropionic acid, and glutathione, used for conventional water phase quantum dot preparation. The ligand exchange of the ionic liquid with the water phase quantum dot is adopted, so that the ionic liquid is converted into a quantum dot coated by a ligand, and the stability of single quantum dot is improved; the ionic liquid is an ionic crystal, an inorganic salt crystal is also ionic crystal, the ionic liquid modified quantum dot is capable of matching growth process of inorganic salt crystal, after mixing with inorganic salt, agglomeration among quantum dot is not easily caused, and uniform dispersed solid state quantum dot with high stability is obtained; the particle size of the solid state quantum dot can be adjusted via grinding, so that solid state quantum dot of different optical properties can be obtained.

The invention discloses rare-earth super-hydrophobic coating capable of keeping fluorescence stability in an aqueous solution and a preparation method of the rare-earth super-hydrophobic coating. The preparation method includes the steps of firstly, using a seeded emulsion polymerization method to prepare core-shell nanoparticles with carboxylic on the surface; secondly, dispersing the core-shell nanoparticles in an organic solvent, and then allowing the dispersed core-shell nanoparticles to have complexing reaction with small-molecule ligands and a rare-earth compound to obtain complexing composite nanoparticles; thirdly, evenly dispersing the obtained complexing composite nanoparticles and low-surface-energy polymer particles, then coating on a certain matrix to obtain the super-hydrophobic coating with the micro-nano structure after the solvent volatilizes. The preparation method has the advantages that the rare-earth super-hydrophobic coating prepared by the method can solve the problem that rare-earth materials are prone to quenching when meeting water, the fluorescence strength of the rare-earth super-hydrophobic coating in purified water or the aqueous solution can be kept unchanged, the method is simple, economical and environmentally friendly, and the rare-earth super-hydrophobic coating is promising in application prospect in fields such as fluorescent display equipment and solar cells.

The invention belongs to the technical field of medical chemistry, and relates to a drug screening method, in particular to a method for establishing a virtual screening model and an in vitro testing model of small-molecule inhibitors by taking cathepsin D as a target point. The method comprises the following steps: (1) acquiring, analyzing and processing a three-dimensional structure of cathepsin D protein; (2) establishing and processing a small-molecule database; (3) establishing a computer virtual screening system; (4) applying the computer virtual screening system obtained in the step (3) to screen a small-molecule ligand library obtained in the step (2); (5) predicting absorption, distribution, metabolism, excretion and toxicity (ADME-T). After the method for screening the cathepsin D inhibitors is adopted, six seedling compounds having cathepsin D inhibition activity are finally screened out; the method has the advantages of being rapid, economical and efficient, greatly increases the efficiency and provides a basis for finding the cathepsin D small-molecule inhibitors. The compounds, which are obtained by using the method and have the cathepsin D inhibition activity, can be further used for developing novel anti-cancer drugs.

The invention discloses a method for fast screening a topoisomerase I inhibitor from a natural product, and relates to the analysis field of natural products. The method comprises the following steps of: (1) preparation of an enzyme binding reaction buffer solution; (2) preparation of a to be detected sample; (3) preparation of a standard solution; (4) binding reaction of the to-be-detected sample and normal and inactive topoisomerase I; (5) chromatography-mass spectrometry detection analysis of reaction sample; and (6) enrichment ratio of the topoisomerase I to the inhibitor. The ultrafiltration membrane technology and the chromatography-mass spectrometry united technology united method are applied to the screening of the topoisomerase I inhibitor, the sample analysis speed is fast and the specificity is strong so as to conveniently recognize a medicine ligand combined with a biological target molecule; meanwhile, the sample analysis dosage is less, and the spectrogram information quantity is large so as to realize the fast screening of the lead compound, the method has great advantage on the aspect of researching mutual effect of medicine small molecule ligand and biological macromolecule receptor; the method is suitable for analyzing in-vitro enrichment ratio of the natural product extract or monomer compound to the topoisomerase I inhibitor.

The invention describes an explicit solvent all-atom molecular dynamics methodology (SILCS: Site Identification by Ligand Competitive Saturation) that uses small aliphatic and aromatic molecules plus water molecules to map the affinity pattern of a large molecule for hydrophobic groups, aromatic groups, hydrogen bond donors, and hydrogen bond acceptors. By simultaneously incorporating ligands representative of all these functionalities, the method is an in silico free energy-based competition assay that generates three-dimensional probability maps of fragment binding (FragMaps) indicating favorable fragment:large molecule interactions. The FragMaps may be used to qualitatively inform the design of small-molecule ligands or as scoring grids for high-throughput in silico docking that incorporates both an atomic-level description of solvation and the large molecule's flexibility.

The invention relates to a preparation method of luminescence rare earth coordination polymer nanoparticles. The luminescence rare earth coordination polymer nanoparticles are obtained through a self-assembly one-step reaction of a biomolecular base, rare earth ions and a micro-molecular ligand by the method. The rare earth coordination polymer nanoparticles prepared in the invention have the characteristics of spherical and porous property, uniform size and composition, luminescence property of the rare earth ions, and good biocompatibility and hydrophilicity. Compared with common preparation methods of the rare earth nanoparticles, the method provided by the invention has the advantages of avoiding of the complex organic synthesis of the ligand, avoiding of an embedding/doping or surface modification/adsorption step, and simplicity. The prepared rare earth nanoparticles have good application prospects in the fields of luminescence display, molecule sensing, tracing imaging, drug delivery and the like.

The invention discloses a precious metal/paramagnetic metal composite nanoparticle with a core-shell structure and application thereof. A preparation method for the precious metal/paramagnetic metal composite nanoparticle comprises the following steps: (a) preparing a precious metal nanoparticle with a particle size of 5 to 50 nm, wherein the precious metal is gold or silver; (b) taking a compound A containing a mercapto group and an amino group, allowing the precious metal nanoparticle to react with the compound A so as to obtain a product a and then allowing the product a to react with methyl acrylate so as to obtain a product b; (c) taking a compound C containing an azido group and an amino group and reacting the product obtained in the step (b) with the compound C so as to obtain an azido-surface-modified precious metal nanoparticle; (d) subjecting the azido-surface-modified precious metal nanoparticle prepared in the step (c) and a micromolecular ligand containing an alkynyl group to the Clicker reaction so as to obtain a product d; and (e) reacting the product d with a chloride of a paramagnetic metal so as to obtain the composite nanoparticle. The precious metal/paramagnetic metal composite nanoparticle can be used as an MRI and CT enhancement contrast agent.

The invention discloses DNA functional gold nano-clusters (AuNCs) and a preparation method thereof. According to the technical scheme of the AuNCs, chloroauric acid serves as a gold source, single-stranded DNA, with the base number being smaller than 60, of 5' end modified sulfydryl serves as a nucleic acid type macromolecule ligand, sulfhydryl water-soluble small organic molecules serve as a small organic molecule ligand, under the alkaline solution condition, sodium borohydride serves as a reducing agent to conduct a reduction reaction, and thus the AuNCs are prepared. The technical scheme of the AuNCs has the advantages that the blanks of products related to existing AuNCs and the preparation technology of the AuNCs are filled.

The invention belongs to the filed of spandex material preparation and in particular relates to a fluorescence modification process for a spandex material. The process comprises the following steps of firstly performing graft polymerization of an intermediate monomer used for complexing rare earth ions on the surface of spandex by virtue of an ultraviolet surface grafting method; and then directly complexing rare earth ions with fluorescence performance (and a coligand) on the spandex subjected to grafting modification. In the modified spandex obtained by the preparation method, a small molecule ligand and a spandex matrix are firmly and stably combined, so that the combination degree of rare earth and the spandex matrix is effectively enhanced, the fluorescence property is effectively improved, and the fluorescent spandex is quite convenient to recycle.

The invention relates to a method for fast discovering lead compounds targeting Bcl-2 protein, which comprises the following steps of: 1) determining a combined site of the Bcl-2 protein and processing a three-dimensional structure; 2) establishing a small molecular ligand library for virtual screening; 3) establishing a computer virtual screening system aiming at the Bcl-2 protein; and 4) primarily determining 10 compounds having higher affinity with active sites by screening the mall molecular ligand library in the step 2) by using the step 3). By the method, the compounds with potential activity can be discovered in a short time, so the efficiency is greatly improved, and a basis is provided for researching and developing a novel anti-cancer medicament, namely a Bcl-2 inhibitor.