12 results about "Small molecule binding" patented technology

This application provides a method for screening inhibitors targeting CYP7A1 and their use in the preparation of anti-liver cancer drugs, relating to the field of tumor targeted drug design technology. The method for screening inhibitors targeting CYP7A1 protein includes: using the crystal structure of human cholesterol 7α-hydroxylase as a receptor model, precise docking screening is performed using software to screen drug-like molecules with molecular weights of 250-500 Da and lipid-water partition coefficients of -1 to 5 from a compound database; a graph neural network active learning model is used to predict and rank the protein-small molecule binding affinity of compounds in the database; the ΔG between candidate molecules and CYP7A1 is calculated using molecular mechanics / generalized Born surface area methods, with molecules having ΔG ≤ -40 kcal / mol considered potential inhibitors. The inhibitors of this application do not rely on the enzymatic activity of CYP7A1 to achieve anti-tumor effects and do not significantly affect cholesterol and bile acid metabolism levels.

The application provides a mass spectrometry detection device and method for active protein-small molecule interaction, which uses a mass spectrometry sensor to obtain tandem mass spectrometry data of non-covalent complexes of active protein incubated with small molecule compounds at different concentration points; performs non-linear curve fitting on the concentration sequence of the small molecule compounds based on the ion combination rate of the protein binding small molecules at each concentration point, to obtain an apparent dissociation constant of the active protein-small molecule interaction; determines a local conformation change parameter of the active protein induced by small molecule binding and a potential binding domain of the small molecule; and performs fusion evaluation on the binding strength and conformation influence degree of the protein-small molecule interaction based on the apparent dissociation constant, the local conformation change parameter and the potential binding domain, to output a stability grade of the protein-small molecule interaction. Based on the above scheme, non-denatured state mass spectrometry detection of protein-small molecule complexes in a liquid phase environment can be realized.

A high-throughput screening system and method for small molecule-protein interactions includes first immobilizing selected small molecules on a solid matrix. Immobilization is preferably performed via photoaffinity labeling, where a linker is used to bind the small molecule to the matrix. cDNA libraries are constructed based on various human tissues. Tissue mRNA is transcribed into cDNA and transferred to a phage genome to construct a phage display library, which is then mixed with small molecules conjugated to microspheres and incubated. The incubated mixture is washed to remove unbound phages, including non-specific and weakly bound phages. Bound phages are amplified and used for the next round of biopanning. The biopanning cycle is repeated, and then PCR is performed on each plaque obtained from the final round of biopanning. The PCR products from each small molecule experiment are barcoded, merged, and then subjected to next-generation sequencing.

This invention relates to the field of anti-aging drug technology, specifically to the application of small molecule compounds in the preparation of anti-aging drugs. These small molecule compounds competitively block the interaction between KDM6A and the vacuolar ATPase V0 domain subunit ATP6V0C by targeting a specific small molecule binding pocket of the histone demethylase KDM6A, thereby inhibiting the demethylation activity of KDM6A on lysine residue 36 of ATP6V0C. These small molecule compounds can effectively downregulate aging-related β-galactosidase activity, improve cell cycle arrest, and reverse the senescent phenotype of nerve cells induced by the environmental pollutant GenX, making them particularly suitable for combating premature aging of nerve cells induced by perfluorinated and polyfluoroalkyl compounds such as GenX. This technical solution can solve the technical problem of the lack of drugs with clearly defined components, a clear mechanism of action, stable efficacy, and the ability to specifically alleviate aging in existing technologies, and has ideal prospects for widespread application.

Small molecules for targeting the 5'UTR to modulate oncogenic protein expression levels and methods thereof are described. These small molecules are inhibitors of BMI 1 expression and may be useful in the treatment of cancer. Also disclosed are small molecule probes to map binding sites and small molecule binding.

In certain examples, methods and apparatuses are directed to small molecules (e.g., drug-like molecules) binding to a target protein in live cells. In a specific example, a method includes: processing a laser beam, from a quantum cascade laser (QCL), carrying light in a wavelength range that overlaps a mid-IR range; using optics, in response to the laser beam, to process the light in a set of related beams along respective paths, including a reference path and a sample path, respectively towards a reference target and a sample target that includes living cells: and detecting, via a vibrational spectroscopy detector, small molecules binding to a target protein in live cells. The detection is carried out by collecting incident light, relative to the reference target and from the sample target, carried along respective incident paths and by discerning (e.g., measuring) vibrational probe frequency shifts in the sample target.

This application relates to the field of biomedical technology, proposing a compound that targets and degrades RALBP1 protein, its preparation, and its application. The compound is the compound shown in formula (I), or its tautomers, stereoisomers, hydrates, solvates, pharmaceutically acceptable salts, or prodrugs. The compound of this application belongs to the PROTAC drug category, which can target small molecule conjugates of RALBP1, thereby inducing RALBP1 degradation and achieving effective prevention or treatment of acute myeloid leukemia. Simultaneously, the compound of this application can be used in oral formulations; through structural optimization, it balances drug activity and oral convenience. Single or multiple administrations can produce significant tumor-suppressive effects, demonstrating broad application prospects. (I)

This application belongs to the field of biotechnology, specifically relating to a method for identifying the binding sites of proteins and small molecules. This application utilizes ultrafiltration to effectively separate double-enzyme digestion products, simplifying sample processing, reducing sample complexity, and lowering the difficulty of data analysis, resulting in more efficient and accurate mass spectrometry data interpretation. Compared to existing restriction enzyme-based methods, this application, through double-enzyme digestion technology, can capture more subtle differences in the binding of proteins and small molecules, improving the accuracy of target protein identification.

The invention belongs to the field of intelligent biological prediction, and particularly relates to an RNA-small molecule binding affinity prediction method based on multi-view learning. The method comprises three stages of data set up and down sampling processing, feature construction and extraction based on RNA and small molecule sequences, and binding affinity prediction. According to the method, data set distribution is optimized through an up-down sampling method, multi-view feature information is constructed through sequence information of RNA and small molecules, a deep network is established to extract and depth biological information features, and finally, an MLP regression device is adopted to predict an RNA-small molecule binding affinity value, so that drug discovery work is assisted to be achieved. In order to solve the problem of imbalance of the existing data set, the invention provides a method of combining up and down sampling for processing, and the problem of imbalance is effectively relieved.

The application discloses a pathogenic Vibrio Pir B virulence protein binding peptide P2 and application thereof. The small-molecule binding peptide P2 has high affinity with the Pir B virulence protein and has an amino acid sequence of LGSPLLTYGRPQ. The application screens the binding peptide with high affinity with the pathogenic Vibrio Pir B virulence protein from a random peptide library through phage display technology, and the binding peptide is chemically synthesized. After injection of the binding peptide, the survival rate of shrimps after infection with Vibrio can be effectively improved, and the shrimps have a remarkable protection effect in shrimp culture. The binding peptide can efficiently bind to the pathogenic Vibrio Pir B virulence protein, and effectively reduce the virulence of the Pir B protein. In addition, the method can effectively reduce the use of antibiotics in healthy shrimp culture, reduce the generation of drug-resistant strains, and has a good application prospect in the prevention and treatment of shrimp AHPND.

The application relates to a small molecule peptide for detecting an endogenous retrovirus K capsid protein and application thereof. The amino acid sequence of the small molecule peptide is shown as SEQ ID NO. 6. The designed HERV-K CA small molecule binding peptide is fused with nanoluciferase (Nanoluciferase, NLuc) for expression, can be specifically combined with the CA protein of the endogenous retrovirus K, and the affinity reaches 10 ‑7 M provides a solution for detecting the CA protein of a human serum or tissue sample, and has better detection efficiency compared with the existing HERV-K Gag antibody for immunodetection of the HERV-K CA protein of a human serum.

Disclosed are a small molecule binding ligand of a α-synuclein aggregate, and a preparation method therefor and a use thereof. The small molecule binding ligand of a α-synuclein aggregate is a compound shown in the following general formula (I). The compound can specifically and strongly bind to a α-synuclein aggregate and can be used for detecting / dyeing the α-synuclein aggregate and Lewy body in the brain of a patient, and a radioactive marker of the compound can be used as an imaging tracer probe required in image examination technologies such as PET and SPECT for clinical disease diagnosis. The compound is further used for preparing the radioactively marked imaging tracer probe or a composition thereof. Diseases associated with α-synuclein misfolding and abnormal aggregation comprise Parkinson's disease, Parkinson's disease dementia, Alzheimer's disease, multiple system atrophy, Lewy body dementia, etc.