770 results about "Binding site" patented technology

The present invention provides a combination of (i) an immune checkpoint modulator and (ii) a T-cell redirecting multifunctional antibody, or an antigen binding fragment thereof, for use in therapeutic treatment of a cancer disease. The T-cell redirecting multifunctional antibody comprises (a) a specificity against a T cell surface antigen; (b) a specificity against a cancer- and / or tumor-associated antigen; and (c) a binding site for human FcγRI, FcγRIIa and / or FcγRIII, wherein the antibody, or the antigen binding fragment thereof, binds with a higher affinity to human FcγRI, FcγRIIa and / or FcγRIII than to human FcγRIIb.

The invention relates to the field of protein-polypeptide interaction prediction in bioinformatics, in particular to a protein-polypeptide binding site prediction method based on graph attention and multi-head attention. The method mainly comprises the following steps: (1) collecting protein and polypeptide compound PDB structure information from an RCSB PDB database, and extracting sequence information of the protein and polypeptide compound PDB structure information; (2) extracting protein sequence information by using IUPred2, ProtBERT and ESM-2 (Extensible Subscriber for Mobile Communications); a ProtBERT method and an Integer method are used for extracting polypeptide sequence information; the method comprises the following steps: extracting protein structure information through biopython; (3) establishing a GAT model with residual connection to analyze a protein structure, and extracting features between amino acid nodes; (4) constructing a Circulate Block module, and carrying out deep extraction and fusion on protein and polypeptide information through four layers of Mti-head Attention and Dual Attention; and (5) finally, through a Final Attention, a linear layer and a Softmax layer, mapping the features to two dimensions to represent the interaction probability of each residue site.

The invention relates to an organic molecule for the application in optoelectronic devices. According to the invention, the organic molecule hasa first chemical moiety with a structure of Formula I:anda second chemical moiety with a structure of Formula II:wherein W is the binding site of a single bond linking the first chemical moiety to the second chemical moiety,L is selected from a direct bond and a linking group with a structure of Formula BN-I:wherein the dashed lines denote the binding sites as indicated in Formula I, and # represents the binding site of the first chemical moiety to the second chemical moiety.

The invention discloses a drug target binding affinity prediction method based on multi-scale feature fusion, and the method comprises the steps: introducing the multi-scale structural features of atoms, atomic groups and molecular levels in the expression of drug molecules, and combining a graph neural network and a sequence modeling module as a feature extractor; and deep interaction and fusion between different scale features of the protein and the drug are realized by using a multi-head bilinear cross attention mechanism, so that potential binding site information is effectively captured, and the accuracy and interpretation capability of affinity prediction are improved. The method not only overcomes the problems that a traditional machine learning method depends on manpower and is low in efficiency in feature construction, but also solves the technical bottlenecks that an existing deep learning method is only limited to local neighborhood information and cannot model global structural features, and the interaction relationship modeling capability is insufficient due to direct splicing of drugs and protein representation.

Reported herein is, inter alia, a method for producing a trivalent bispecific antibody, the method comprising the steps of culturing a mammalian cell comprising a deoxyribonucleic acid encoding the trivalent bispecific antibody, and recovering the trivalent bispecific antibody from the cell or culture medium, wherein the deoxyribonucleic acid encoding the trivalent bispecific antibody is stably integrated into the genome of the mammalian cell and comprises in the 5' to 3' direction a first expression cassette encoding a first heavy chain, a second expression cassette encoding the first heavy chain, a third expression cassette encoding a first light chain, a fourth expression cassette encoding the first light chain, a fifth expression cassette encoding the second heavy chain, a sixth expression cassette encoding the first light chain or the second heavy chain or the second light chain, and a seventh expression cassette encoding the second light chain, wherein the first heavy chain The chain comprises, from N-terminus to C-terminus, a first heavy chain variable domain, a CH1 domain, a hinge region, a CH2 domain, a CH3 domain, a peptide linker, a second heavy chain variable domain and a CL domain, the second heavy chain comprises, from N-terminus to C-terminus, a first heavy chain variable domain, a CH1 domain, a hinge region, a CH2 domain and a CH3 domain, the first light chain comprises, from N-terminus to C-terminus, a first light chain variable domain and a CH1 domain, and the second light chain comprises, from N-terminus to C-terminus, a second light chain variable domain and a CL domain, wherein the second heavy chain variable domain and the first light chain variable domain form a first binding site, and the first heavy chain variable domain and the second light chain variable domain form a second binding site.

The invention relates to the technical field of protein prediction, in particular to a protein binding site prediction method based on geometric deep learning. According to the method, protein geometric description and a corresponding geometric diagram learning scheme are introduced, and a feasible way is provided for modeling three-dimensional structural features; in addition, the invention also provides an RSA-guided two-stage hybrid transfer learning strategy, firstly, a model is trained on a larger data set to learn general representation, and then fine tuning is carried out for binding site prediction, so that the overfitting problem in limited data training is relieved; according to the invention, a prediction post-processing module and an integrated learning module based on density clustering are designed, and the high variance of the model in multiple times of training operation is significantly reduced.

The invention provides an antibody drug conjugate property prediction method based on multi-modal fusion, and belongs to the field of bioinformatics. The method comprises the following steps: firstly, explicitly modeling sequence position information through sine position coding; secondly, introducing a bidirectional cross attention mechanism to establish interaction between a light chain and a heavy chain and alignment between an antigen and an antibody; thirdly, the integrated graph neural network reconstructs the adjacency relation according to the attention weight, and topological features are extracted; and finally, in combination with a double-stage self-adaptive refining module, two-stage treatment of alignment and refining is realized, and each modal feature contribution is adjusted in a self-adaptive manner. And meanwhile, the sequence robustness is improved through Mask perception feature extraction, and the interpretability analysis of the key binding sites is realized through the attention weight. The method can significantly improve the prediction accuracy, and can be widely applied to cancer targeted therapy and drug design optimization.

The invention discloses a preparation method of Fe3O4 magnetic nanoparticles rich in carboxyl groups on the surface, which comprises the following steps: modifying Fe3O4 nanoparticles by using polyethylene glycol and silicon dioxide to enhance the dispersity and biocompatibility of the magnetic nanoparticles, modifying the surfaces of PEG-Fe3O4 coated SiO2 nanoparticles by using a silane coupling agent containing silane groups and unsaturated double bonds to obtain the magnetic nanoparticles rich in carboxyl groups on the surface, and modifying the magnetic nanoparticles rich in carboxyl groups on the surface by using a silane coupling agent containing silane groups and unsaturated double bonds to obtain the magnetic nanoparticles rich in carboxyl groups on the surface. Then octavinyl-POSS and double bonds on the surfaces of the nano particles are subjected to click modification to form an octahedral cage, 4-mercaptobenzoic acid and double bonds are further subjected to click modification, the surfaces of the nano particles are rich in carboxyl, and a polymer brush rich in carboxyl is constructed. Compared with a conventional streptavidin coupling method, a high-density polymer chain provides a large number of carboxyl active binding sites, so that the streptavidin coupling amount is increased, the antibody coupling rate is increased, and a solution is provided for applications such as high-sensitivity biological detection, efficient targeted drug delivery and stable immunoassay.

The invention discloses a biotin ligase mutant and application thereof, and belongs to the technical field of gene engineering. According to the invention, a series of biotin ligase mutants are prepared by docking biotin ligase and substrate molecules thereof and carrying out multiple mutations on screened 10 amino acids with binding force acting sites. On the basis, a biotin ligase mutant is connected to escherichia coli through a homologous recombination technology, a series of escherichia coli recombinant bacteria with high biotin yield are obtained, and the biotin yield reaches 0.873 mg / L to the maximum after 24-hour fermentation.

The invention relates to a UGT enzyme subtype substrate specificity prediction method and model. On the basis of a directional message passing neural network, graph structure characterization of a small molecule compound and features of specific protein binding sites of UGT enzyme are deeply fused, a bimodal prediction normal form of'molecule + protein binding sites' is designed, a deep learning model is constructed, conversion from compound center prediction to molecule-enzyme binding site comprehensive prediction is achieved, and the prediction accuracy is improved. And accurate classification prediction can be carried out on UGT enzyme substrates and non-substrates.

The invention discloses a deep learning prediction method fused with multi-modal features, which can accurately identify protein hidden binding sites in a ligand-free (apoo) state. The method comprises the following steps of: firstly, constructing a protein graph by taking residues as nodes and taking C alpha distance less than or equal to 14 as edges, wherein node feature sets comprise amino acid one-hot, secondary structures, atomic attributes, protein language model embedding and BLOSUM62 evolutionary information, and edge features comprise distance and angle similarity; then capturing three-dimensional geometric equivariant features by adopting an equivariant graph neural network (EGNN), and modeling a chemical topological relation by using a graph isomorphic network (GINE) with edge features; eGNN and GINE double-branch feature fusion and global dependence integration are realized through gating cross attention and gating multi-head attention; and finally, inputting the fusion features into a Kolmogorov-Arnold network (KAN) classifier, and predicting whether each residue belongs to a hidden binding site or not. The method can adapt to large-scale conformation change without coordinate alignment, AUC and F1 on a standard data set are remarkably superior to those of an existing method, high robustness and generalization are kept for multi-chain protein and complex conformation, and the method can be widely applied to drug target discovery and structure-driven drug design.

Multispecific antibody having a binding site for ICOS and a binding site for a second antigen, e.g., an immune checkpoint molecule such as PD-L1. Use of the multispecific antibody in immuno-oncology, including for treatment of solid tumours.

96 New PCT-Patent Application based on EP 24 186 635.9 Insempra GmbH Vossius Ref.: AG4141 PCT S3 Abstract The present invention relates to a linear double-stranded deoxyribonucleic acid (dsDNA) molecule comprising one or more Tus protein (Tus) binding site(s) at the 5'-terminus, one or more Lac repressor protein (LacI) binding site(s) at the 3'-terminus, and a segment comprising a DNA sequence of interest (DOI) between said Tus binding site(s) and said LacI binding site(s). The present invention further relates to a non-naturally or naturally occurring RNA molecule as encoded by or transcribable / transcribed from the linear dsDNA molecule of the invention, and to an expression DNA cassette comprising a promoter, an RBS, a GOI encoding a POI, and one or more LacI binding site(s), wherein said expression cassette does not comprise a terminator sequence between the 3´ end of said GOI and said one or more LacI binding site(s). The present invention also relates to a non-naturally or naturally occurring RNA molecule as encoded by or transcribable / transcribed from said expression cassette. The present invention further relates to method of protecting a linear deoxyribonucleic acid (DNA) molecule from exonuclease degradation by adding one or more Tus binding site(s) at the first terminus of the DNA molecule and adding one or more LacI binding site(s) at the other terminus of the DNA molecule. The present invention further relates to a method of synthesizing a protein of interest (POI) in a cell- free protein synthesis (CFPS) reaction mixture by using the (ds)DNA and / or RNA molecules of the invention, and also to a cell-free biological system or CFPS reaction mixture comprising the (ds)DNA, expression cassette and / or RNA molecules of the invention.

The invention discloses injection type facial filler composition gel for medical beauty as well as a preparation method and application of the injection type facial filler composition gel, and belongs to the technical field of biomedical materials. The composition gel comprises a combined gel matrix and polycaprolactone microspheres, wherein the combined gel matrix comprises an aqueous solution for injection, sodium carboxymethyl cellulose and human recombinant collagen; according to the composition gel, a combined gel matrix and polycaprolactone microspheres are mixed according to a specific proportion, amino acid residues of human-derived recombinant collagen in the combined gel matrix serve as binding sites of cell surface receptors to improve the cell recognition and attachment capacity of the polycaprolactone microspheres, and the amino acid residues are organically combined with sodium carboxymethyl cellulose to improve the cell recognition and attachment capacity of the polycaprolactone microspheres. The durability and biocompatibility of the shaping effect of the human-derived recombinant collagen at the injection site are improved; the composition prepared by the invention is good in gel fluidity, high in elastic modulus and high in dynamic viscosity, and can meet the expected mechanical and rheological properties of a facial filling agent for cosmetic and plastic surgery.

The invention relates to a DNA framework structure addressable enzyme ligation method. Specifically, the invention provides a method for accurately regulating and controlling the specific position of an enzyme on a DNA frame structure through an enzyme modification and base complementary pairing principle, and provides a frame nucleic acid with a capture segment and an enzyme with a connecting chain, and the frame nucleic acid with the capture segment and the enzyme with the connecting chain are subjected to base complementary pairing through the connecting chain and the capture segment. Therefore, the enzyme is connected to a predetermined binding site of the framework nucleic acid, and accurate regulation and control of the connection position, number spacing and the like of the enzyme on the framework nucleic acid are realized. The connection method provided by the invention can realize addressable and accurate enzyme position regulation and control on the DNA nano structure, can widen site-specific modification of the enzyme on the DNA frame structure, and has important significance for developing site-specific and high-throughput enzymatic reaction.

Disclosed are systems and methods for detecting extracellular ligands and / or inducing expression of an exogenous or endogenous gene. The disclosed systems and methods typically include and / or utilize (i) first and second exogenous extracellular sensors, and third and fourth exogenous extracellular sensors; and (ii) an expression vector comprising a target gene operably linked to a hybrid promoter sequence. The hybrid promoter sequence of the expression vector includes a minimal promoter for inducing transcription and the hybrid promoter sequence further includes interspaced transcription regulator binding sites upstream of the minimal promoter that bind two or more transcription regulators of the extracellular sensors that are released from the extracellular sensors when the extracellular sensor bind an extracellular ligand.

The present invention relates to: a receptor tyrosine kinase like orphan receptor 1 (ROR 1) antibody or an antigen-binding fragment thereof; a nucleic acid encoding same; a recombinant expression vector carrying the nucleic acid; a host cell transinfected with the recombinant expression vector; a method for preparing the antibody or the antigen-binding fragment thereof; a bi- or multi-specific antibody bearing the antibody or the antigen-binding fragment thereof; an immune cell-engaging bi- or multi-specific antibody; an antibody-drug conjugate (ADC) in which the antibody or the antigen-binding fragment thereof is bound to a drug; a chimeric antigen receptor (CAR) containing the scFv of the antibody as an antigen-binding site of an extracellular domain; an immune cell having the chimeric antigen receptor introduced thereinto; a composition for combination therapy including the antibody or the antigen-binding fragment thereof; a composition for preventing or treating cancer; and a method for preventing or treating cancer.

An engineered producer cell comprising an inactivating mutation in one or more endogenous REP binding sites is provided, as are methods for producing the engineered producer cell and using the engineered producer cell to produce a recombinant viral vector and reduce producer cell genomic DNA contamination of a recombinant adeno-associated virus vector preparation.

The invention provides a protein and metal ion binding site identification method, device and equipment, and belongs to the field of protein detection.The method comprises the steps that feature extraction is conducted on known metal ion binding protein, and multiple sample evolution information features are obtained; the method comprises the following steps: for an unknown protein sequence, determining candidate distant homologous metal ion binding proteins through multi-sequence comparison and cosine similarity screening, and further constructing a training set; a composite framework in which a bidirectional long-short-term memory network and a full-connection neural network are connected in series is adopted, input features comprise evolutionary information features and physicochemical attribute features, and probability values of binding sites of different metal ions are output; training the composite framework through the training set to obtain a site prediction model; and predicting a binding site of an unknown protein sequence by using the prediction model. The stable and efficient prediction on the metal ion binding site is realized.

The invention discloses an eggshell membrane peptide for enhancing bone mineral density as well as a preparation method and application thereof, belongs to the technical field of egg by-product processing, and particularly relates to a preparation method of the eggshell membrane peptide for enhancing bone mineral density, which comprises the following steps: carrying out vacuum freeze drying and crushing on an eggshell membrane to obtain eggshell membrane powder; mixing the eggshell membrane powder with deionized water to obtain an eggshell membrane solution; adding keratinase, performing enzymolysis, and taking supernate; adding collagenase, carrying out enzymolysis, and centrifuging to take supernate, so as to obtain primary enzymatic hydrolysate; adding alkaline phosphatase, performing enzymolysis and centrifugation, and taking supernate to obtain enzymatic hydrolysate; and performing ultrafiltration and drying to obtain the eggshell membrane peptide. According to the eggshell membrane peptide for enhancing the bone mineral density, keratin cross-linking is destroyed through enzymolysis of keratinase, active peptide capable of stimulating osteoblast proliferation is released through enzymolysis of collagenase, phosphopeptide calcium binding sites are further activated through enzymolysis of alkaline phosphatase, calcium salt deposition is promoted, and the eggshell membrane peptide for enhancing the bone mineral density is provided.

A computer-implemented method for identifying a consensus molecular sequence from full length and partial length read sequencing data of a sample. The method includes sorting the sequencing data into full length and partial length reads with 5' and / or 3' binding sites, clustering the full length reads and the partial length reads, the clustering based on a position of binding site(s), and comparing a partial length read cluster to a full length read cluster to determine a positional distance between the compared clusters. In response to determining that the positional distance between the compared clusters falls within a redetermined threshold, merging the compared clusters, and identifying a consensus molecular sequence of the sample based on the merged clusters.

The invention discloses recombinant humanized XVII type and recombinant humanized I type collagen sequences as well as a synthesis method and application thereof, the recombinant humanized collagen comprises one or more functional sequences in cell integrin binding sites such as R / KGD, GER / K, GVMGFP and DGEA, the molecular weight is 6-14 kDa, and the recombinant humanized collagen simultaneously surrounds an isoelectric point, has hydrophilicity and hydrophobicity, and can be used for preparing the recombinant humanized collagen. Reasonable design is carried out on information such as an antigen epitope, GXY sequence stability, protease degradation sites and the like, so that the recombinant humanized collagen has relatively good stability and also has biological activity of promoting cell proliferation and resisting wrinkles and tightening.

The invention relates to bispecific antibodies comprising a first antigen-binding site that specifically binds to PD1 and a second antigen-binding site that specifically binds to TIM3, in particular to bispecific antibodies, wherein the bispecific antibody binds to 5 TIM3 with a lower binding affinity when compared to the binding to PD1. The invention further relates to methods of producing these molecules and to methods of using the same.

The invention belongs to the technical field of molecular biology, and particularly relates to a DNA binding site of a fungus transcription factor AniJ and application. According to the invention, an echinocandin B gene cluster regulatory factor AniJ is taken as a research object, a ptH-SpRY-ACBE base editor and an sgRNA library covering an aniA promoter are utilized, 5-FOA screening is combined, and a binding motif RNGCTGAS of the AniJ in a core promoter region is excavated. The construction of an engineering strain containing a modified promoter (increasing the number of motifs) proves that the motifs can significantly enhance the expression of aniA and the yield of echinocandin B. And a novel molecular tool is provided for metabolic engineering of natural products of fungi.

The invention provides a method for improving the stability of fermented milk through ultrasonic-polysaccharide synergism and the fermented milk, and relates to the technical field of dairy products. The method comprises the following steps: performing ultrasonic treatment on a mixture of homogenized and sterilized raw milk and sodium alginate to obtain a fermentation base material, wherein the ultrasonic treatment conditions are as follows: the ultrasonic treatment power is 144-240W, the frequency is 20-40kHz, and the treatment time is 4-10min. Sodium alginate is added into raw milk, the stability of the fermented milk is improved through ultrasonic-polysaccharide synergism, when ultrasonic breaks a long chain of sodium alginate, casein binding sites are specifically activated, and an egg box structure is efficiently induced to be formed, so that a more compact and stable three-dimensional network gel structure is constructed; the product quality and the storage stability of the fermented milk are improved.

Provided herein are compositions comprising trispecific and / or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins or one or more T-cell receptors, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation and wherein a second pair of polypeptides forming the binding protein possess a single variable domain. Also provided herein are methods for making trispecific and / or trivalent binding proteins and uses of such binding proteins for the treatment and / or prevention of HIV / AIDS.

Provided are a method for constructing a soluble expression plasmid mutant library, and the use thereof. The method for constructing the soluble expression plasmid mutant library comprises: introducing mutations into a ribosome binding site on a soluble expression plasmid, a sequence composition and length of a region between the ribosome binding site and an initiation codon of a fusion protein to be expressed, and a translation initiation region, so as to obtain a mutant library. By means of the method, plasmid mutants with increased expression levels are obtained, thereby increasing the expression level of a target fusion protein and the final yield of a target polypeptide. The present invention solves the problem of low soluble expression levels of certain polypeptides in Escherichia coli.

This invention generally relates to a novel RNA / mRNA production and amplification method using viral RNA replicase and / or RNA-dependent RNA polymerase (RdRp) enzymes as well as the associated mRNAs thereof. The present invention can be used for manufacturing and amplifying all varieties of RNA / mRNA sequences carrying at least an RdRp-binding site in the 5′- or 3′-end, or both. The RNA / mRNA so obtained is useful for not only producing mRNA vaccines and / or RNA-based medicines but also for generating the mRNA-associated proteins, peptides, and / or antibodies under an in-vitro as well as in-cell translation condition. Principally, the present invention is a novel RNA replicase-mediated RNA / mRNA amplification method, namely Replicase Cycling Reaction (RCR). The RNA replicases involved in RCR include but not limited to viral and / or bacteriophage RNA-dependent RNA polymerases (RdRp), particularly coronaviral and hepatitis C viral (HCV) RdRp enzymes.

The invention discloses trichosanthes kirilowii maxim seed polypeptide with alpha-glucosidase inhibitory activity and a preparation method thereof. Four Trichosanthes kirilowii Maxim seed polypeptides with alpha-glucosidase inhibitory activity are obtained through Trichosanthes kirilowii Maxim seed protein preparation, enzymolysis, separation and purification and identification, and the sequences of the four Trichosanthes kirilowii Maxim seed polypeptides are respectively HRQTWD, HANRLP, FGGVGER and SYAPEDR. Molecular docking analysis results show that interaction between the trichosanthes kirilowii maxim seed hydrolytic peptide and amino acid residues of an alpha-glucosidase active pocket is mainly based on hydrogen bonds, electrostatic interaction and hydrophobic interaction, and residues D203, D327, D443, F450, D542 and F575 are key binding sites interacting with the four polypeptides. The trichosanthes kirilowii maxim seed polypeptide with alpha-glucosidase inhibitory activity prepared by the invention can be used as a food-borne hypoglycemic component to be used for developing health-care foods and medicines for reducing blood sugar.

The invention belongs to the technical field of biochemical detection, and particularly relates to a micro-fluidic chip PSMA prostate cancer circulating tumor cell immunoenrichment detection kit and a preparation method thereof. According to the kit, an EpCAM antibody, a Vimentin antibody and a double-site PSMA capture combination are fixed in a chip channel through a streptavidin-biotin system, double enrichment of epithelial and mesenchymal CTCs is achieved, PSMA targets are recognized through combination of an aptamer and the antibody, and the detection specificity and sensitivity are improved. Competitive oligopeptides are further introduced to block non-specific binding sites on the surfaces of leukocytes and reduce false positive. By combining a multiple fluorescent chromosome system and a double-antibody nucleic acid probe signal amplification strategy, accurate recognition and quantification of CTC and PSMA positive cells are realized. The scheme is suitable for early screening, curative effect evaluation and relapse monitoring of prostate cancer, and has a good clinical application prospect.