63 results about "Scaffold protein" patented technology

Small molecule therapeutics can concentrate in distinct intracellular environments, some bounded by membranes, and others that may be formed by membrane-less biomolecular condensates. The chemical environments within biomolecular condensates have been proposed to differ from those outside these bodies, but the internal chemical environments of diverse condensates have yet to be explored. Here we use small molecule probes to demonstrate that condensates formed in vitro with the scaffold proteins of different biomolecular condensates harbor distinct chemical solvating properties. The chemical rules that govern selective partitioning in condensates, which we term condensate chemical grammar, can be ascertained by deep learning, allowing efficient prediction of the partitioning behavior of small molecules. The rules learned from in vitro condensates were adequate to predict the partitioning of small molecules into nucleolar condensates in living cells. Different biomolecular condensates harbor distinct chemical environments, that the chemical grammar of condensates can be ascertained by machine learning.

A nanomedicine composition, preparation method, and use thereof, comprising: a negatively charged nanophospholipid disk and an antimicrobial compound; wherein the negatively charged nanophospholipid disk comprises a negatively charged phospholipid layer and a membrane scaffold protein, wherein the negatively charged phospholipid layer is formed by mixing a neutral phospholipid and a negatively charged phospholipid in a molar ratio of approximately 5:5-7:3. The nanomedicine composition provided herein reduces the toxicity of the antimicrobial compound while enhancing its antimicrobial efficacy, and has great potential for expansion into clinical applications.

The present invention relates to an exosome scaffold protein and the use thereof. PVR protein is used as an exosome scaffold protein to load effective substances, such that the loading capacity and the loading efficiency of the effective substances are improved. In addition, the exosome scaffold protein can also be used for loading larger and more structurally complex effective substances.

The present invention relates to an exosome scaffold protein and the use thereof. PVR protein is used as an exosome scaffold protein to load effective substances, such that the loading capacity and the loading efficiency of the effective substances are improved. In addition, the exosome scaffold protein can also be used for loading larger and more structurally complex effective substances.

The invention relates to a method for regulating and controlling the phase separation capacity of protein and application thereof. The method comprises the following steps: mixing a first protein element and a second protein element to obtain a mixture; detecting the phase separation capacity of the mixture; wherein the first protein element comprises an IDR structural domain of the scaffold protein, and the second protein element comprises a self-assembly structural domain of the scaffold protein or the IDR structural domain of the scaffold protein. According to the method, the IDR structural domain of the scaffold protein is used as the first protein element, the self-assembly structural domain of the scaffold protein or the IDR structural domain of the scaffold protein is used as the second protein element, and the first protein element and the second protein element interact with each other, so that the phase separation strength of the protein elements can be accurately regulated and controlled; and physical or chemical factor intervention is not needed, so that the compatibility between the regulation process and the normal physiological function of the cell is ensured. The method for regulating and controlling the phase separation capacity of the protein has relatively high controllability and biocompatibility.

A macromolecular interaction regulator screening method, comprising the steps of: providing an engineered cell, the cell containing a target condensate A having dynamic fluidity, the target condensate A containing a first fusion protein formed by a target molecule X, a phase separation scaffold protein Y and a first fluorescent protein F1 module, the cell further co-expressing a second fusion protein, and the second fusion protein being a fusion protein formed by a target molecule B and a second fluorescent protein F2 module; by means of interaction of the target molecule X and the target molecule B, forming a condensate complex A-B; in the presence or absence of a candidate compound, separately performing photobleaching treatment on the cell, and measuring fluorescence signals obtained before and after the photobleaching treatment of the condensate complex A-B in the cell; and performing comparison for the change of the fluorescence signals, and evaluating the impact of the candidate compound on the interaction of the target molecule X and the target molecule B.

Nanolipoprotein particles having at least a scaffold protein component and a membrane lipid component and related compositions, methods and systems are described. The membrane lipid component includes at least one or more membrane forming lipids, one or more polymerized lipids and / or one or more polymerizable lipids.

The present invention relates to proteins suitable for being used as scaffolds to which a peptide of interest is bound, or which are comprised within a conjugate to which an agent of interest is attached. It also relates to said conjugates suitable for the selective delivery of their conjugated agents of interest to specific cell and tissue types, wherein said agent can be a therapeutic agent or an imaging agent. It also relates to nanoparticles comprising such conjugates and the therapeutic uses thereof.

The invention relates to an engineered extracellular vesicle with an anti-inflammatory effect and a preparation method of the engineered extracellular vesicle. The engineered extracellular vesicle comprises an extracellular vesicle, an arginase 1 mutant located in a cavity of the extracellular vesicle, an internal support protein for connecting the arginase 1 mutant with the extracellular vesicle, and an external support protein for connecting the internal support protein with the extracellular vesicle, the arginase 1 mutant comprises an arginase 1 protein and a trimer tag, the C end of the arginase 1 protein is connected with the trimer tag, and the N end of the arginase 1 protein is connected with the C end of an endogenous scaffold protein. The engineered extracellular vesicle disclosed by the invention is high in loading efficiency and good in delivery effect, has multi-target activity and has an enhanced broad-spectrum anti-inflammatory effect.

This invention relates to antibody-binding lipid nanoparticles comprising antibodies bound to membrane scaffold proteins, and more specifically, to antibody-binding lipid nanoparticles comprising lipids and antibodies bound to membrane scaffold proteins, which are therefore easy to prepare and have excellent specific targeting capabilities.

The invention discloses a bone targeting exosome polypeptide delivery system based on a biological orthogonal strategy and a preparation method and application thereof, and relates to the technical field of biological medicine and drug delivery. The bone targeting exosome polypeptide delivery system based on the biological orthogonal strategy comprises an engineered exosome as a carrier and an osteogenesis-promoting therapeutic polypeptide, wherein the osteogenesis-promoting therapeutic polypeptide is anchored on the membrane surface of the engineered exosome; a fusion protein is displayed on the membrane surface of the engineered exosome, and the fusion protein is formed by fusing a bone targeting ligand and an industrial exosome transmembrane scaffold protein; the osteogenesis-promoting therapeutic polypeptide is connected with the industrial exosome through the flexible spacer arm, and the membrane surface steric hindrance is reduced through the flexible spacer arm so as to improve the accessibility of the active fragment of the polypeptide; the delivery system provided by the invention can improve the targeted enrichment and treatment efficiency of osteogenesis promoting drugs in bone tissues, and is suitable for intervention of bone metabolism related diseases such as osteoporosis, delayed fracture healing, bone defects and the like.

Protein scaffolds and scaffold libraries based on a fibronectin type III (FN3) domain with an alternative binding surface design, isolated nucleic acids encoding the protein scaffolds, vectors, host cells, methods of making thereof, and uses as therapeutic molecules for treatment and diagnosis of diseases and disorders.

The invention belongs to the field of new auxiliary materials and new dosage forms of pharmaceutical preparations, and relates to a preparation method and application of a co-assembled nano preparation for targeting glioblastoma. The preparation method comprises the following steps: firstly, synthesizing a nitroimidazole dimer with tumor hypoxia-oxidation-reduction triple response, and assembling the nitroimidazole dimer with AOH1996 and HRO761 to prepare the nano preparation. The molar ratio of the AOH1996 to the HRO761 to the nitroimidazole dimer is 1 to 2 to (0.5 to 2). The key scaffold protein PCNA for DNA repair is blocked by the PCNA inhibitor AOH1996, and recruitment and anchoring functions of the key scaffold protein PCNA on repair factors are destroyed, so that the glioblastoma is induced to enter a mismatch repair defect state. On the basis, a WRN inhibitor HRO761 is further used for promoting large-scale breakage of chromosomes and finally inducing cell death. The nitroimidazole dimer and the nitroimidazole dimer are jointly assembled into the nano preparation, and accurate drug release is realized in response to a hypoxia state and oxidation and reduction signals overexpressed in a tumor microenvironment, so that the heterogeneity of the tumor microenvironment is overcome.

The invention relates to a method for regulating and controlling the phase separation capacity of protein and application thereof. The method comprises the following steps: mixing a first protein element and a second protein element to obtain a mixture; detecting the phase separation capacity of the mixture; wherein the first protein element comprises an IDR structural domain of the scaffold protein, and the second protein element comprises a self-assembly structural domain of the scaffold protein or the IDR structural domain of the scaffold protein. According to the method, the IDR structural domain of the scaffold protein is used as the first protein element, the self-assembly structural domain of the scaffold protein or the IDR structural domain of the scaffold protein is used as the second protein element, and the first protein element and the second protein element interact with each other, so that the phase separation strength of the protein elements can be accurately regulated and controlled; and physical or chemical factor intervention is not needed, so that the compatibility between the regulation process and the normal physiological function of the cell is ensured. The method for regulating and controlling the phase separation capacity of the protein has relatively high controllability and biocompatibility.

The application discloses application of SCAMP5 in treatment of autism spectrum disorder. The application research proves that, compared with a CON group, VPA-induced ASD rats have significant neurotransmitter release disorder and synapse signal path abnormality in hippocampus, overexpression of SCAMP5 protein can improve abnormal release of Glu, abnormal expression of scaffold protein Homer1b / c and downstream protein IP3R, and meanwhile, can relieve autism-like behaviors, space working memory and synapse development abnormality of ASD rats. The application provides a new target and a new potential drug for treatment of autism spectrum disorder, and provides a new idea for target treatment of ASD by in-depth exploration of potential path in pathogenesis of autism.

The invention provides a chicken tibia strength character molecular genetic marker, and relates to the technical field of poultry genetic engineering breeding. The molecular genetic marker of the chicken tibia strength character is a 390 site SNP of an intron 5 of a chicken Cas scaffold protein family member 4 gene, the SNP site is located at the 203th site of SEQ ID NO: 1, and the polymorphism of the SNP site is G / A. The genotype of the molecular genetic marker is obtained by carrying out PCR amplification and sequencing on primers F: 5 '-CCGTCATGCCTACAAG-3' and R: 5 '-GGGATGTTTCACGGGAGGA-3'. The molecular genetic marker is applied to chicken tibia intensity character auxiliary selective breeding, and can realize early selection of tibia intensity characters and early elimination of unwanted breeding hens, so that the feeding cost is reduced, and the chicken tibia intensity character breeding progress is accelerated.

The present invention relates to a drug delivery carrier based on extracellular vesicles and its application. The drug delivery carrier contains an extracellular vesicle scaffold protein and a recombinant membrane fusion protein. The recombinant membrane fusion protein includes a first fragment and a second fragment. The amino acid sequence of the first fragment is the amino acid sequence shown in SEQ ID NO:5, and the second fragment has n amino acids, and the sequence of the second fragment is the sequence of the first n amino acids at the N-terminus of the amino acid sequence shown in SEQ ID NO:7, where n is an integer between 50 and 200. The efficiency of releasing drug active molecules by the drug delivery carrier of the present invention before reaching lysosomes is significantly improved, and the efficacy of extracellular vesicle-based drugs can be enhanced.

The present disclosure relates to methods of removing lipids (e.g., cholesterol) or preventing lipid accumulation in an eye of an individual (e.g., a human), and methods of preventing or treating an eye disease characterized by lipid accumulation (e.g., age-related macular degeneration) in an individual, such as an eye disease characterized by age-related macular degeneration. The method comprises administering to an eye of an individual an effective amount of a pharmaceutical composition comprising a plurality of nanodisks, wherein the nanodisks comprise a membrane scaffold protein (MSP) and a phospholipid.

The present disclosure provides scaffold proteins that serve as framework regions for different sets of complementarity determining regions (CDRs) from source antibodies, where the source antibodies bind to different epitopes. The scaffold proteins find use in generating antigen binding polypeptides in single chain fragment variable (scFv) antibody format from a variety of antibodies of interest. These antigen binding polypeptides can have one or more advantageous properties as compared to a source antibody, such as, increased affinity, increased stability, increased expression in a cell, increased yield, etc. The sequence of a scaffold protein has a sequence identity of less than 68% to the sequence of the framework regions of the source antibody.

The invention relates to the field of bacterial membrane protein structures. More specifically, the invention relates to lipid nanodiscs compartmentalized by SlyB protein oligomers isolated from the outer membrane of Gram-negative bacteria. More specifically, the invention provides for a SlyB nanodisc structure wherein the SlyB-oligomer forms the membrane scaffold protein belt, which is surrounded by outer saccharolipid moieties anchored to the SlyB proteins, and which encloses a lipid bilayer nanodomain containing one or more phospholipid layers, wherein macromolecules such as (outer) membrane protein molecules may be captured and stabilized. More specifically, methods to produce and isolate chemically defined stable SlyB nanodisc particles are disclosed herein. Finally, the invention relates to the use of said SlyB nanodiscs as a self-adjuvanting vehicle, as part of an immunogenic composition, and provides for novel means for use in eliciting an immune response against macromolecules enclosed in said SlyB nanodiscs, or for use in a vaccine composition.

The present invention relates to one or more binding molecules capable of inducing receptor signaling of a receptor complex under conditions of non-competitive and / or two-site binding to a scaffold protein. The invention also relates to the therapeutic use of said one or more binding molecules in cancer and autoimmune diseases.

The present invention relates to genetically modified extracellular vesicles comprising an improved scaffold protein and a protein of interest. Also disclosed are related polypeptide compositions, polynucleotide compositions, cells, pharmaceutical compositions, and methods.

The present application provides a method for protein structure analysis using cryo-EM, comprising: including a tag in a target protein; combining the target protein including the tag with a scaffold protein to form a complex of the target protein and the scaffold protein; and using a cryo-EM for single particle imaging to analyze the structure of the target protein complexed with the scaffold protein. The scaffold protein is any one of streptavidin, avidin or a derivative thereof. The tag is used to selectively bind to the scaffold protein. The tag is selected from one of the following group: a biotin tag including biotin; a biotinylated protein or polypeptide tag including a protein sequence and biotin covalently linked to the protein sequence; a streptomyces tag (Strep-tag); and a biotinylated or streptococcal labeled antibody, antibody Fab fragment or single chain antibody.

This invention provides a method for designing scaffold proteins that mediate RuBisCO aggregation in crop plants. Using a known scaffold protein as a template, this method generates sequences through the following steps: a. RFdiffusion scaffold protein backbone generation; b. MPNN sequence generation; c. AlphaFold structure prediction; and d. Optimizing the optimal sequence by evaluating the generated scaffold protein sequences using one or more scoring metrics. Unlike previous research focused on RuBisCO itself, this invention shifts the focus to the design and optimization of scaffold proteins. By optimizing the parameter evaluation method for protein design, novel scaffold proteins were designed, addressing the bottleneck of traditional methods in forming the RuBisCO concentration module and opening up a new research direction.

Disclosed are methods for obtaining cells that express antibodies that bind transmembrane proteins, methods for generating antibodies from such cells, antibodies to transmembrane proteins and fragments thereof, and nucleic acids encoding the antibodies. More particularly, the disclosure relates to methods for obtaining antibody-producing cells that express an antibody that binds to a transmembrane protein based on the use of lipid bilayer-membrane scaffold protein complexes to present transmembrane protein antigens to cells.

The invention discloses a candida tropicalis engineering bacterium for producing 1, 2, 4-butantriol as well as a construction method and application of the candida tropicalis engineering bacterium, and belongs to the technical field of microorganisms. According to the recombinant candida tropicalis strain constructed by the invention, scaffold protein ligand-enzyme fusion protein is subjected to integrated expression through metabolic engineering transformation, and a scaffold protein structural domain GBD-SH3-PDZ is overexpressed on the basis of the scaffold protein ligand-enzyme fusion protein; a glucose repression gene MIG1 gene is knocked out; the KdcA mutant is subjected to overexpression, the yield of 1, 2, 4-butantriol can be obviously increased, the shake flask yield of 1, 2, 4-butantriol is increased to 2.1 g / L from 0.6 g / L of the original strain BTO-01, the yield is increased by 3.35 times, and the yield of the strain BTO-14 in a 5L tank reaches 11.18 g / L through amplification culture of a fermentation tank.

The invention relates to a polypeptide, such as an Affimer polypeptide, comprising an amino acid sequence having at least 80% identity to amino acid residues 1 to 11, 13 to 15, 17 to 19, 21 to 25, 27 to 28, 35 to 37, 39, 41, 43 to 44, 46 to 47, 49 to 50, 52 to 53, 55 to 58, 63 to 64, 66, 68 to 82, 84 to 85, and 87 to 98 of SEQ ID NO: 1; characterized in that said polypeptide comprises one or mutations relative to SEQ ID NO: 1. The invention also relates to various methods and nucleic acids.

The invention discloses yarrowia lipolytica genetically engineered bacteria for producing lutein as well as a construction method and application of the yarrowia lipolytica genetically engineered bacteria. According to the invention, the Cu < 2 + > induced promoter pMT2 is introduced, and the lycopene is differentially regulated on the time scale to carry out epsilon-cyclization reaction and beta-cyclization reaction, so that the content of by-product beta-carotene is greatly reduced; by introducing a cipB scaffold protein strategy, a high-efficiency electron transport protein complex for converting alpha-carotene into xanthophyll is constructed, and the content of an intermediate product alpha-cryptoxanthin is effectively reduced; by introducing a synthetic route of cytochrome P450 monooxygenase cofactor heme, the activity of a key catalytic enzyme is improved, and the yield of xanthophyll is effectively improved. The Yarrowia lipolytica engineering strain can utilize common carbon sources and nitrogen sources, the shake flask yield of xanthophyll can reach 93 mg / L after fermentation culture, and the Yarrowia lipolytica engineering strain is an excellent strain with high xanthophyll yield and has great industrial application prospects.

Systems and polypeptide complexes are provided that combine scaffold protein modules with a variety of effector modules, enabling comprehensive and versatile control at the protein, RNA, and DNA levels. In addition, uses of them in the modulation of gene expression and potential uses in the treatment of disease are provided.

The invention provides a novel reverse aldolase and reductase cascaded Bi-BDO independent synthesis pathway, and relates to the technical field of bioengineering, the pathway constructs a non-natural metabolism module composed of a modified reverse aldolase RA variant, 4-hydroxybutyraldehyde reductase AHR and a coenzyme cyclic regeneration enzyme, the RA variant performs hydrophobic modification on a Lys146 site, and the reverse aldolase and reductase cascaded Bi-BDO is obtained. Aldol condensation of a non-phosphorylated substrate hydroxyacetaldehyde is realized to generate a C4 intermediate, RA and AHR are physically anchored by utilizing an artificially synthesized scaffold protein, toxicity of the intermediate is avoided through a substrate channel effect, the intermediate is instantly reduced into 1, 4-butanediol, engineering bacteria of aldA and gapA genes are knocked out, a precursor is generated by utilizing a xylose way, and the 1, 4-butanediol is obtained. The method has the advantages that the method is simple in operation, the reduction reaction is driven by in-situ regeneration of NADPH by adding formate, finally, the high-purity product is obtained through macroporous adsorption resin enrichment and vacuum rectification, the TCA circulation decarboxylation step is omitted, the carbon conversion rate is close to the theoretical limit, effective decoupling of production and growth is achieved, and the yield and purity of Bi-BDO are remarkably improved.