110 results about "Ligand molecule" patented technology

The invention discloses a two-dimensional bionic nanostructure assembled based on receptor-ligand acting force and a preparation method of the two-dimensional bionic nanostructure. The core characteristic of the two-dimensional bionic nanostructure is that the ultrafine particles modified by ligand molecules are anchored on the surface of a cell membrane fragment with a corresponding receptor expressed on the surface through a receptor-ligand effect, so that uniform compounding of the ultrafine particles and the cell membrane is realized; the bottlenecks of low compounding efficiency, functional site masking and the like caused by high surface curvature of small-size particles in the traditional cell membrane complete wrapping technology are broken through. According to the preparation method disclosed by the invention, the binding force between the cell membrane and the ultramicro particles is stronger, the off-target phenomenon of the ultramicro particles in the in-vivo circulation process can be avoided, the response release of the ultramicro particles under the competition effect in a lesion region expressed by a high-abundance receptor can be realized, and the preparation method has a good application prospect in the aspect of precise drug delivery. Meanwhile, the in-vivo circulation time of the ultrafine particles is prolonged by membrane loading, the biocompatibility of the ultrafine particles is improved, and the effectiveness and low toxicity of a drug delivery system are ensured.

The invention relates to a UCNPs probe-based in-situ dynamic monitoring molecular interaction method, which comprises: S1, providing a UCNPs probe, the core layer of the UCNPs probe being a rare earth up-conversion nanocrystal, the shell layer of the UCNPs probe being an anti-quenching inert material, and the anti-quenching inert material coating the surface of the rare earth up-conversion nanocrystal; the surface of the anti-quenching inert material is modified with ligand molecules, and the ligand molecules are used for being specifically combined with target molecules in a to-be-detected sample; s2, mixing or contacting the UCNPs probe with a to-be-detected sample containing target molecules to construct a to-be-analyzed molecular interaction system; s3, irradiating the molecular interaction system by adopting near-infrared pulse laser, and collecting the change of the fluorescence lifetime tau of the UCNPs along with the time t and the change of the fluorescence intensity I along with the time t in real time to obtain a tau-t curve and an I-t curve; and S4, according to the tau-t curve and the I-t curve, realizing in-situ dynamic monitoring on the molecular interaction state. According to the method, a molecular binding / dissociation event is directly converted into a quantifiable and anti-interference optical signal, and the technical defect that in-situ dynamic monitoring of molecular interaction cannot be achieved in a traditional technology is overcome.

The invention provides a rare earth complex as well as a preparation method and application thereof. The chemical general formula of the rare earth complex is (Ln < 1x > Ln < 2y > Ln < 31-x-y >) (A) m (B) n, the rare earth complex provided by the invention has a self-assembly behavior, spherical nanoparticles can be formed through molecular aggregation, under ultraviolet irradiation, internal ligand molecules are better protected, the photobleaching process of the rare earth complex under natural conditions is slowed down, and the rare earth complex has better stability and higher weather resistance in the natural environment.

The embodiment of the invention discloses a protein-ligand interaction prediction method and a related device. Determining a prediction interaction pair formed by atoms of the protein and atoms of the ligand molecule according to the data of the protein and the data of the ligand molecule, establishing a loss function according to the node characteristics and the edge characteristics of the real interaction pair and the node characteristics and the edge characteristics of the prediction interaction pair, and adjusting model parameters according to the loss function, the target neural network model can be used for predicting the interaction between any protein and ligand molecules. Physical priori knowledge of protein-ligand interaction is fused in model training and prediction, so that the model can learn characteristics with more biological significance, and the predicted biological correlation is improved. According to the method, the advantages of deep learning are utilized, high-dimensional features are automatically extracted, complex pattern recognition is carried out, the complex relation in protein-ligand interaction is captured, and the stability and accuracy of protein-ligand interaction prediction are improved.

The application belongs to the technical field of food safety detection, and specifically discloses a method for detecting BaP in edible oil by using CTAB modified silver nanomaterial based on LLE-SERS, which comprises the following steps: preparing Ag nanoparticle sol, preparing CTAB functionalized Ag nanoparticle sol, SERS detection of BaP standard aqueous solution with different concentrations, fitting a standard curve, extracting BaP and performing SERS detection. The synthetic raw materials of the surface CTAB functionalized Ag nanoparticles used in the application are simple, and the coverage degree of the ligand molecules CTAB on the surface of the Ag nanoparticles can be controlled and adjusted. The CTAB as the surface ligand can directly capture and enrich BaP molecules. The detection method is high in stability, and can effectively avoid the problem that different batches of samples produce different effects in the Raman test.

The application discloses a kind of based on active fragment's targeted ligand generation method, including fragment sequencing process: based on fragmentation method and sequencing method processing ligand molecule for training obtains fragment sequence;Model training process: ligand molecule fragment sequence and target protein amino acid sequence for training are input into targeted ligand molecule generation model, the molecular representation of ligand molecule fragment sequence is extracted by fragment sequence encoder, and the target representation of target protein amino acid sequence is extracted by target encoder, feature fusion is used after fragment sequence decoder output fragment sequence, and optimization model;Targeted ligand molecule generation process: target protein amino acid sequence is input into the model after training, the target representation is extracted by target encoder, and compound information is predicted by priori network and is input into fragment sequence decoder, and output fragment sequence, again based on molecular reconstruction method fragment sequence is recombined into targeted ligand molecule.

This invention discloses a method for preparing cerium phytate complexes and their biological applications. A cerium ion aqueous solution is added to a phytic acid aqueous solution under stirring, and stirring continues until precipitation is complete. The mixture is then washed with ultrapure water until the washing solution is neutral, filtered, and dried to obtain a cerium phytate complex with a porous nanostructure. This invention utilizes a method for preparing cerium phytate complexes with the above-described structure and their biological applications, without using organic solvents, making the synthesis process safe and environmentally friendly. Phytic acid, as a ligand molecule constituting cerium phytate, has six phosphate groups, which can efficiently coordinate with cerium ions to form cerium phytate materials, exhibiting good thermal stability and ultraviolet absorption. The cerium phytate nanoparticles formed by the coordination of phytic acid and cerium ions carry a large amount of Ce. 3+ This is the basis for the antioxidant activity of cerium phytate. At the same time, the numerous pores inside the material effectively promote the adsorption of reactive oxygen free radicals, giving it highly efficient antioxidant properties, which can be applied to the treatment of various diseases related to reactive oxygen species.

The application relates to the field of medicinal chemistry and provides a use of a diphenylacetonitrile compound and a protein-targeting hydrolytic chimeric compound. The application finds that a diphenylacetonitrile compound shown in formula (I) directly interacts with FEM1B, thereby serving as an inhibitor of a human E3 ubiquitin ligase substrate recognition receptor FEM1B. The application also provides a compound shown in formula (II), and the compound shown in formula (II) is a protein-targeting hydrolytic chimeric (PROTAC) drug, wherein Q2 is a target protein ligand molecule, Q1 is a FEM1B inhibitor, Q2 is combined with a target protein, thereby inducing E3 ligase FEM1B combined with Q1 to approach the target protein, leading to ubiquitination and degradation of the target protein. Experimental results show that the PROTAC drug shown in formula (II) provided by the application can specifically degrade a target protein in cells. Formula (I); formula (II).

The invention discloses a ligand molecule generation method based on multi-modal information guidance, which fully captures high-precision interaction between a protein pocket and a ligand molecule, not only considers structural information of the ligand molecule, but also performs sufficient information guidance aiming at a protein target point molecule generation method. The generated molecules have diversity, and the requirements of subsequent biological docking experiment verification are met; on the other hand, the potential interaction relationship between the protein structure characteristics and the ligand molecules is utilized, different protein targets are fused in the diffusion process, and various modal information is balanced to guide the generation of the ligand molecules.

The invention relates to a multi-metal zinc complex, a preparation method and application in polymer depolymerization. The multi-metal zinc complex forms a stable coordinate bond with an organic ligand molecular skeleton, shows excellent chemical stability and substrate adaptability, and can efficiently catalyze the depolymerization reaction of various polymers in a temperature range of 100-250 DEG C. In addition, the ligand framework has adjustability, polymer substrates with different compositions and structures can be optimized, and high-yield recovery of various types of monomers is realized. The catalytic system has wide applicability, can catalyze the bulk depolymerization of the polymer, and also can catalyze the depolymerization in the presence of a nucleophilic reagent. Through a multi-metal concerted catalysis mechanism, the dosage of the catalyst is remarkably reduced, various polymers with the number-average molecular weight in the range of 3.8-807.5 kg / mol can be depolymerized, the depolymerization reaction time is 0.5-24.0 h, side reactions are remarkably inhibited, and excellent industrial application prospects are shown.

The application discloses a preparation method of a rare earth coordination type force-induced multi-fluorescent color variable gel, and comprises the following steps: dissolving a Schiff base ligand molecule, a monomer, an initiator and a crosslinking agent in deionized water, and stirring uniformly to obtain a stable solution, wherein the monomer is at least one of acrylamide, ethyl acrylate, methyl acrylate and methacrylic acid; adding a rare earth compound into the stable solution to obtain a prepolymer solution, and obtaining the rare earth coordination type force-induced multi-fluorescent color variable gel through free radical polymerization; the method has mild conditions, simple steps and is easy to realize. The application further discloses the force-induced multi-fluorescent color variable gel prepared through the preparation method; the types of the rare earth ions and the Schiff base ligand molecules are adjusted to obtain a multi-color fluorescent gel, and the visual fluorescent color change is realized under the action of external force. The force-induced multi-fluorescent color variable gel is combined with other functional materials to realize the integration of multiple functions, and can be applied to multiple fields such as optical devices and mechanical sensors.

The objective is to provide a novel method for improving the efficiency of osteogenic differentiation induction based on immobilized BMP-2. [Solution] A method for stimulating cells with ligand molecules, comprising a stimulation step of applying physical stimulation to the cells and / or ligand molecules, wherein the ligand molecule is bound to or interacts with a receptor protein expressed on the cells and is immobilized on a culture substrate and / or matrix molecule used for culturing the cells, the receptor protein mediates the transmission of extracellular signals to the cells based on its binding to the ligand molecule, and the extracellular signals are enhanced by the physical stimulation.

This invention relates to the field of molecular docking technology, and discloses a method and system for screening female reproductive drugs in reproductive medicine. The method includes: constructing a female reproductive drug screening platform for target female users; defining a data parsing algorithm for the user interface; parsing reproductive examination data and reproductive needs into physiological parameters of the target user; mapping physiological states to relevant target proteins; retrieving molecular data of relevant target proteins; and matching ligand molecules of relevant target proteins. The method also includes: culturing target cells in vitro; adding ligand molecules to the in vitro cultured tissue; detecting cell activity, gene expression, and protein expression in the ligand test tissue; analyzing the enhancing effect of the ligand molecules on the ligand test tissue; calculating the gain coefficient of the enhancing effect; screening the optimal ligand molecules; and determining the female reproductive drugs for the target female users. This invention can improve the efficiency and accuracy of female reproductive drug screening in reproductive medicine.

The application discloses a kind of bivalent ligand molecules for targeting BCL6 protein degradation and application thereof, it is related to the technical field of drug development;The structure general formula of the bivalent ligand molecules for targeting BCL6 protein degradation is as follows: M1-L-M2;Wherein, M1 and M2 are independent structure same or different BCL6 protein ligand;L is any chain or cyclic hydrocarbon fragment capable of forming covalent bond with BCL6 ligand.The application also provides the application of the bivalent ligand molecules in the preparation of anti-tumor and / or immune disease drugs.The bivalent ligand molecules can exert good anti-tumor activity on a variety of BCL6-dependent tumors by selectively inducing BCL6 protein degradation, and are also related to the occurrence of a variety of immune diseases, and can be used in related tumor and immune disease drugs.

The present invention belongs to the field of clinical diagnostic technology and relates to a method for preparing an aptamer biosensor for rapid detection of dual tumor markers. The present invention prepares a composite nanofiber membrane of polyacrylonitrile and transition metal salt precursors based on a coaxial electrospinning process. The carbon nanofiber structure uniformly loaded with cobalt metal nanoparticles obtained by a thermal reduction method has a large specific surface area and a unique three-dimensional network electron transmission channel, which significantly improves the electron transfer capacity and the loading amount of aptamer molecules. The biosensor based on the core-shell nanofiber network structure exhibits excellent electrocatalytic ability and signal stability. The preparation process of the biosensor is simple and controllable, and it is easy to achieve large-scale and productized production. It can realize the rapid identification and detection of trace miRNA-155 and miRNA-21 nucleic acid molecules in real serum within 2 minutes, and has important application value in disease diagnosis and clinical biomedicine.

The invention discloses a pharmaceutical composition for treating tumors and application thereof. According to the invention, the BrTAC with anti-tumor activity is constructed by adopting a specific branched skeleton and ligand molecules such as pomalidomide and BI 2536, and the degradation efficiency of target protein PLK1 can be greatly improved. Fluorescence imaging results prove that BrTAC can induce liquid-liquid phase separation in cells, and in-vivo experiment results show that compared with traditional bivalent PROTAC, BrTAC has a better effect in the aspect of PLK1 degradation.

The invention discloses a molecular fragment library based on protein binding site properties and a construction method and application thereof, and belongs to the field of computer-aided drug design. The construction method comprises the following steps: acquiring three-dimensional structure data of a protein-ligand compound, and preprocessing to obtain standardized protein binding sites and ligand molecules; cutting the standardized ligand molecules by adopting an iterative molecular cutting algorithm to generate molecular fragments; identifying and quantifying an interaction between the molecular fragment and an amino acid residue in the normalized protein binding site; and associating the molecular fragments, the information of the amino acid residues interacting with the molecular fragments and the corresponding interaction modes, and constructing a molecular fragment library. The interaction mode of molecular fragments and specific amino acid residues is labeled, so that the targeting property of the fragment library is improved; and the candidate fragments with specific interaction potential can be quickly positioned, so that the drug design efficiency is improved.

The present invention addresses the problem of providing a novel method for increasing bone differentiation induction efficiency based on immobilized BMP-2.　Provided is a method for stimulating a cell with a ligand molecule, the method including a stimulation step for applying a physical stimulus to the cell and / or the ligand molecule. The ligand molecule binds to or interacts with a receptor protein expressed on the cell, and is immobilized on a culture substrate and / or a matrix molecule used for culturing the cell. The receptor protein mediates the transmission of an extracellular signal to the cell on the basis of binding to the ligand molecule, and the extracellular signal is enhanced by the physical stimulus.

This invention discloses an EGCG supramolecular compound with antioxidant, liver-protective, and fat-reducing effects, its preparation method, and composition. The supramolecular compound is formed by non-covalent bonding between epigallocatechin gallate (EGCG) and ligand molecules containing trimethylamine and carboxyl groups; the supramolecular compound has a co-amorphous structure; the ligand molecules containing trimethylamine and carboxyl groups are betaine, ergothioneine, or L-carnitine. This invention can solve the problems of low stability and bioavailability of EGCG. It can significantly improve the solubility of EGCG and its ligands, including betaine, L-carnitine, and ergothioneine, reduce the hygroscopicity of EGCG and its ligands, including betaine, L-carnitine, and ergothioneine, and enhance the stability and bioavailability of EGCG and its ligands, including betaine, L-carnitine, and ergothioneine.

The invention provides a method for inhibiting the efficiency roll-off of a quantum dot light-emitting diode, and the method comprises the following steps: coating or depositing a quantum dot solution on an electron transport layer or a hole transport layer to prepare an LED, and enabling quantum dots to form a single-layer film structure; ligand molecules are arranged on the surfaces of the quantum dots; the distance between at least two quantum dots in the quantum dot LED with the single-layer film structure is d, and d is greater than the sum of the maximum lengths of two ligand molecules. The efficiency roll-off of the quantum dot light-emitting diode can be inhibited.

The invention discloses a novel nuclear magnetic resonance contrast agent Gd-DOTA-PP for targeting citrullinated histone to achieve neutrophil extracellular trap net imaging and a preparation method and application thereof.The method comprises the steps that citrullinated histone targeting polypeptide PP and ligand molecules DOTA-NHS are combined, and a compound DOTA-PP is obtained; and then gadolinium (Gd) ions are introduced into the DOTA-PP through a coordination reaction, and the novel contrast agent Gd-DOTA-PP is prepared. The contrast agent can be selectively combined with an important marker, namely citrullinated histone, of neutrophil extracellular trapping nets (NETs), and T1 weighted imaging signals of a target area are remarkably enhanced. The preparation method is simple and convenient to operate, the preparation process is highly controllable, and the obtained contrast agent has excellent biocompatibility and targeting characteristic. The accurate targeting ability of the probe enables the influence signal of the probe in NETs enrichment areas such as tumor early metastasis, tumor infiltration lymph nodes and the like to be obviously enhanced, a powerful tool is provided for tumor diagnosis, especially accurate diagnosis of the early metastasis, and the probe has important clinical application value.

The invention belongs to the technical field of fluorescence sensing, and particularly relates to a zinc-based coordination polymer based on a heterocyclic ligand and a preparation method and application thereof. The method comprises the following steps: dissolving 3, 7-dibromo-10H-phenothiazine, pyridine-4-boric acid and K2CO3 in a mixed solution of DMF (Dimethyl Formamide) and H2O, uniformly stirring, then adding tetrakis (triphenylphosphine) palladium, carrying out a heating reflux reaction under protective gas, removing a solvent after the reaction is finished, separating impurities, and purifying to obtain 3, 7-bis (4-pyridyl) phenothiazine; the preparation method comprises the following steps: preparing a heterocyclic ligand, dissolving the heterocyclic ligand and zinc nitrate hexahydrate in a mixed solution of DMF and H2O, uniformly stirring, heating to react, and washing and drying after the reaction is finished to obtain the zinc-based coordination polymer based on the heterocyclic ligand. According to the present invention, by using the butterfly conformation and electron donating effect of the ligand molecule 3, 7-bis (4-pyridyl) phenothiazine and the coordination binding capacity synergistic effect of pyridine, the ligand molecule 3, 7-bis (4-pyridyl) phenothiazine is coordinated with zinc ions to construct the novel material with excellent luminescence property;

The invention belongs to the technical field of molecular biology and drug screening, and provides a screening method of capsaicin targeting SOCS5-RBMX protein interaction and application of the capsaicin, an SOCS5-RBMX protein complex structure is analyzed, and SOCS5-RBMX binding structural domains and SOCS5-RBMX binding key sites are determined; the effect of inhibiting protein binding is verified through point mutation of the key sites; determining a binding pocket, taking a drug in the ZINC22 small molecule drug database and a drug approved by FDA as ligand molecules, and taking the binding pocket as a docking region for virtual screening to obtain a compound; the obtained compound is screened through AMDET, and the screened medicine for inhibiting SOCS5-RBMX binding is capsaicin; capsaicin is used for carrying out in-vivo and in-vitro experiments for further screening verification; according to the method, the structure of the SOCS5-RBMX protein complex is analyzed, the binding structural domain and the key site are determined, virtual screening and experimental verification are carried out on the basis of the binding structural domain and the key site, the medicine for inhibiting SOCS5-RBMX binding can be accurately screened out, and the accuracy and efficiency of medicine screening are improved.

The invention discloses a nucleic acid aptamer targeting RUNX1 protein and application thereof, and belongs to the technical field of biology, the nucleotide sequence of the nucleic acid aptamer is shown as RUNX1-5, and the nucleic acid aptamer is obtained through an in-vitro screening SELEX (systematic evolution of ligands by exponential enrichment) technology. The nucleic acid aptamer is small in molecular weight, is easy to chemically synthesize and functionally modify, has good physical and chemical stability, shows high affinity to the RUNX1 protein, has a dissociation constant lower than 30 nM, has good application prospects in the aspects of detection, separation and purification, marking and the like of the RUNX1 protein, and can also be used for preparing medicines for treating RUNX1 related diseases.

The application belongs to the technical field of separation and extraction, and particularly relates to a 8C-DAPhen ligand, a preparation method and application thereof. The method is developed from the design of a ligand molecular structure, and a novel cyclic DAPhen ligand is developed through specific structure design. The ligand has a separation factor (SF Eu / Am ) of more than 600 for lanthanide and actinide elements, and exhibits excellent separation performance. The application provides a new perspective for in-depth understanding of lanthanide and actinide separation mechanism, and provides technical support for establishing an advanced spent nuclear fuel reprocessing system and realizing efficient utilization of minor actinide elements.

The application belongs to the technical field of molecular biology and drug screening, and provides a method for screening phenylhydrazine sulfate based on a key binding amino acid site of SOCS5-CP and application thereof, which comprises the following steps: key amino acid sites of SOCS5-CP binding are screened through alanine virtual point mutation, and a binding pocket is determined; a ligand molecule is used to perform virtual screening by taking the binding pocket as a docking area, and a compound with the best binding energy is obtained; the obtained drug is screened through AMDET; the selected compound is used for subsequent in-vitro cell experiments, and further screening is performed; the application uses the method of molecular docking and virtual screening in combination with in-vitro experiments for screening, and finds that phenylhydrazine sulfate can be stably combined at the key amino acid sites of SOCS5-CP, in-vitro experiments show that phenylhydrazine sulfate can effectively inhibit the binding of SOCS5-CP, and further down-regulate the protein expression level of HIF1a in hepatoma cells, and also has a significant inhibitory effect on the invasion and migration ability of primary hepatocellular carcinoma.

Provided is a ligand molecule against bacterial membranes, the ligand molecule including a compound having a ketone, a tertiary amine, and a single bond or an alkylene group spacer between the ketone and the tertiary amine.

The present invention belongs to the field of drug design and specifically discloses a virtual screening method for small molecule inhibitors targeting the YTHDF1 protein, comprising: obtaining the YTHDF1 protein structure and generating multiple conformational proteins through homology modeling; obtaining a small molecule that binds to the YTHDF1 protein and generating a bait molecule to form a ligand molecule; docking the ligand molecule with the binding site on YTHDF1 and characterizing the complex through PLEC fingerprinting; using a machine learning algorithm to construct a specificity scoring function, scoring and screening the complexes of the docked compounds to be screened and the YTHDF1 molecule, and then performing affinity prediction to screen small molecule inhibitors targeting YTHDF1. The virtual screening method provided by the present invention can screen YTHDF1-targeting molecules with high affinity on a large scale and accurately, providing candidate molecules for drug development for YTHDF1-related diseases and laying the foundation for clinical trials and drug optimization.

The invention discloses an alpha-arylation reaction enantioselectivity prediction method based on machine learning. The alpha-arylation reaction enantioselectivity prediction method comprises the following steps: acquiring a reaction data set; calculating a physical and chemical descriptor based on a ligand molecular structure, and carrying out feature screening, standardization and dimension reduction processing on the descriptor to construct low-dimensional feature representation of the reaction; constructing and training a supervised machine learning regression model based on low-dimensional feature representation; and inputting a to-be-predicted ligand structure into the trained machine learning model to obtain a prediction result of the enantioselectivity of the alpha-arylation reaction, and applying the prediction result to virtual screening and optimization of candidate ligands. The method can effectively describe the influence of the ligand structure on the reaction enantioselectivity without depending on complex reaction mechanism assumption, realizes prediction of the enantioselectivity of the asymmetric catalytic reaction, and shows good generalization ability. According to the method, molecular structure characteristic engineering and machine learning modeling are combined, so that the accuracy of enantioselectivity prediction and the ligand screening efficiency are improved.

A protein-ligand blind docking method guided by candidate binding center. The application generates candidate binding center scores according to protein residue nodes, and restructures local pocket sub-graph based on the screening results of candidate binding centers to make candidate binding region positioning results enter the local candidate binding conformation generation process. The application first proposes candidate binding centers based on the full protein multi-level heterogeneous graph, and then reconstructs the local pocket sub-graph around the retained candidate binding centers after screening, so that the local multi-level geometric coding is limited within the local protein environment around the candidate binding center. A multi-level heterogeneous graph containing ligand atom nodes, ligand molecule nodes, protein atom nodes, protein residue nodes and protein context nodes is constructed, and the atom level, protein residue level and context level node information is retained in the local pocket sub-graph, so that the local candidate binding conformation generation process utilizes the atomic local geometric relationship, protein residue structure information and protein context information.