316results about "Transferrins" patented technology

This invention discloses a milk protein containing composition comprising: at least one milk protein; at least a first protein; at least a second protein; and at least a linker comprising an amino acid sequence coded by nucleotide sequence which is at least 80% similar to sequences selected from the group consisting of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, and SEQ ID NO: 21

Aspects of the disclosure relate to methods of reducing expression or activity of DUX4 (e.g., DUX4 protein and / or mRNA) and / or methods of treating facioscapulohumeral muscular dystrophy (FSHD) in a subject. In some embodiments, the methods comprise administering to the subject a composition comprising complexes (e.g., muscle targeting complexes) comprising an oligonucleotide (e.g., an RNAi oligonucleotide such as an siRNA) covalently linked to an antibody (e.g., anti-TfRl antibody).

The invention relates to a preparation method and application of recombinant canine lactoferrin and peptide thereof, aiming at codon preference of host cells, canine lactoferrin genes are optimized, the full length of canine lactoferrin and the lactoferrin peptide are successfully expressed by virtue of an escherichia coli expression system, and the recombinant canine lactoferrin and the peptide thereof are identified by virtue of a minimum inhibitory concentration experiment. It is proved that the canine lactoferrin and the peptide thereof have the inhibiting capacity on pathogenic bacteria such as staphylococcus aureus, salmonella typhimurium and staphylococcus pseudointermedius, and the antibacterial activity MIC of the canine lactoferrin on the staphylococcus aureus, the salmonella typhimurium and the staphylococcus pseudointermedius is 1.5 mg / mL; the antibacterial activity MIC of the dog lactoferrin peptide to staphylococcus aureus is equal to 0.75 mg / mL, and the dog lactoferrin peptide shows high antibacterial ability.

The invention provides a safrole hapten and application of the safrole hapten in detection of safrole through immunoassay. The structure of the safrole hapten is shown in the specification. The two safrole haptens provided by the invention have spacer arms with proper lengths, and after the safrole haptens are coupled with carrier protein, the haptens can be fully exposed, and recognition of the spacer arms can be avoided as much as possible. The safrole hapten is used for preparing an artificial antigen and an antibody, and the obtained safrole monoclonal antibody is high in titer, strong in specificity and high in affinity. An immunoassay method constructed on the basis of the safrole artificial antigen and antibody has high specificity and sensitivity, the lowest detection limit LOD is 0.09 ng / mL, the half inhibitory concentration IC50 is 2.05 ng / mL, the quantitative detection range is 0.28-14.89 ng / mL, no cross reaction exists on safrole analogues, and rapid qualitative and quantitative detection can be conducted on safrole in a sample.

The invention discloses a method for screening high-yield recombinant human lactoferrin through nucleic acid aptamer-assisted mutagenesis of a trichoderma reesei strain and application, and belongs to the technical field of microorganisms. The nucleic acid aptamer Lac-6a-FAM-BHQ1 capable of changing the fluorescence intensity according to the content of lactoferrin is constructed on the basis of the aptamer Lac-6a, and the nucleic acid aptamer can be used for rapidly selecting a mutant strain for producing high-titer recombinant human lactoferrin. The ARTP mutagenesis technology is combined with a nucleic acid aptamer auxiliary screening system, the mutant strain with the improved recombinant human lactoferrin yield is rapidly obtained from a large number of mutant strains, and the yield reaches 274.57 mg / L and is improved by 24.8% compared with that of an original strain. After the genes 111681 and 62716 are over-expressed in T. reesei, compared with a control strain, the yields of the recombinant human lactoferrin of the recombinant strain are respectively increased by 6.9% and 22.1%.

In the first aspect, the present disclosure provides a Lactoferrin polypeptide fragment, where the Lactoferrin polypeptide fragment has an amino acid sequence shown in SEQ ID NO: 1. In the second aspect, the present disclosure provides a preparation method of the Lactoferrin polypeptide fragment, including: protecting amino acids using a 9-fluorenylmethoxycarbonyl (Fmoc) protecting group, coupling the amino acids with a P-hydroxymethylphenoxymethyl polyethylene resin (HMP resin) in an order of cysteine, alanine, leucine, cysteine, glutamate, threonine, asparagine, aspartate, asparagine, phenylalanine, leucine, leucine, asparagine, and lysine, and separating the HMP resin to obtain a target Lactoferrin polypeptide fragment. In the third aspect, the present disclosure further provides an anti-Lactoferrin antibody prepared using the Lactoferrin polypeptide fragment, and use of the Lactoferrin polypeptide fragment in preparation of an anti-Lactoferrin flow cytometric antibody and in preparation of a Lactoferrin detection product.

The invention is applicable to the technical field of molecular biology, and provides a polypeptide specifically bound with a transferrin receptor, the polypeptide comprises a general formula of H1-H2-E1-E2-H3-H4-E3, and H1, H2, H3 and H4 independently comprise an alpha helical domain; the E1, the E2 and the E3 respectively and independently comprise a beta folding structural domain; when the polypeptide is combined with the hTfR1, transferrin is allowed to be combined to the hTfR1; the polypeptides are capable of binding and delivering oligonucleotides. The invention also provides a recombinant nucleic acid encoding the polypeptide, an expression vector comprising the recombinant nucleic acid, a recombinant host cell comprising the polypeptide, the nucleic acid and / or the expression vector, a conjugate of the polypeptide and oligonucleotide, and a corresponding pharmaceutical composition. The polypeptide disclosed by the invention can be highly specifically combined with hTfR1, so that accurate delivery of oligonucleotide is realized, and a practical basis is provided for treating diseases related to gene mutation.

The invention belongs to the field of food nutrition and functional factors, and particularly relates to a method for preparing ovotransferrin hydrolysate with high immunocompetence based on an adult gastrointestinal simulated digestion system. According to the method, ovotransferrin is treated through the stomach and intestine of a simulated adult, OVT hydrolysate is prepared, and the OVT hydrolysate contains HTEGSTT, TTSY and / or RTAGWVIPMG. The invention finds that the immunomodulatory activity of OVT is enhanced after gastrointestinal digestion and hydrolysis, the OVT is more easily hydrolyzed in simulated adult digestive juice than in infant digestive juice, and a contrast experiment shows that the nutrition intervention of OVT adult and infant simulated digestion products can promote the generation of short-chain fatty acids such as acetic acid, propionic acid and butyric acid; the swelling injury caused by inflammation to small intestine mucous membrane tissues is effectively relieved, so that the intestinal barrier immune function is obviously improved, and the OIA shows higher intestinal immune activity than the OIB.

The invention discloses pichia pastoris for efficiently synthesizing lactoferrin as well as a construction method and application of the pichia pastoris, and belongs to the technical field of biosynthesis. The pichia pastoris for efficiently synthesizing the lactoferrin expresses at least one of KAR2, PDI1 and ERO1 in molecular chaperones in a host in an enhanced manner and carries an optimized secretory signal peptide, and the secretory signal peptide is obtained by replacing a leading peptide of alpha-factor with any signal peptide in LacZ, PelB, FLO and alpha-factor. The yield of LF can be effectively increased by enhancing expression of at least one of KAR2, PDI1 and ERO1 molecular chaperones in molecular chaperones in a host; when the lactoferrin expression cassette is integrated into the recombinant pichia pastoris X-33 genome and the copy number is increased to 2-6, the LF yield can be further increased, and when the copy number is 4, the LF yield reaches a peak value.

The invention provides an analgin hapten, a preparation method thereof, an artificial antigen, an antibody and application. The structures of the analgin haptens are as shown in a formula (I) or a formula (II), the two analgin haptens provided by the invention have spacer arms with proper lengths, and after the two analgin haptens are coupled with protein, the haptens can be fully exposed to an immune system, the spacer arms can be prevented from being recognized as much as possible, and a better antibody is generated to recognize analgin. The analgin hapten is used for preparing artificial antigen and antibody, the obtained analgin monoclonal antibody has high titer and strong specificity, an immunoassay method constructed based on the analgin monoclonal antibody has high specificity and sensitivity, analgin in a sample can be rapidly, qualitatively and quantitatively detected, the operation is simple and convenient, and the detection result is accurate and reliable.

The present invention relates to novel enzyme nanoparticles capable of converting methane into methanol, in which key active sites of methane-oxidizing bacteria are fused with each other and expressed on a protein that can be self-assembled in cells to form nanoparticles, and specifically to enzyme nanoparticles including a protein having methane monooxygenase (MMO) activity and active sites of the methane oxidase, a method for production thereof, a recombinant microorganism into which a nucleic acid encoding the protein and the active site of the methane oxidase is introduced, and immobilized enzyme nanoparticles including the enzyme nanoparticles loaded on a carrier.

The invention discloses an enhancer regulatory element for transcriptional regulation expression of a human LTF gene and application of the enhancer regulatory element. The sequence of the regulatory element is SEQ ID No.1. Experiments prove that the human specific regulatory element can significantly activate report gene expression (improved by 14.93 times) in a bovine mammary epithelial cell line (MACT), the limitation of dependence on species conservative elements in the prior art is broken through, and an expression system designed based on the element can realize human level LTF high-efficiency expression. And a brand new tool is provided for development of mammary gland bioreactors and functional dairy products.

The present invention relates to a ferritin nanocage fused with PD-L1-binding peptide 1 and a use thereof as an anticancer immunotherapy agent. Prepared in the present invention were nanocages that are formed by fusing a human ferritin monomer with a peptide 1 (PD-L1pep1: CLQKTPKQC) binding to the immune checkpoint receptor PD-L1 overexpressed in many cancers such as breast cancer, colorectal cancer, renal cancer, glioblastoma, etc. and which display 24 Pd-L1prep1. The nanocages of the present invention effectively target colorectal cancer tissues to exhibit an anticancer effect. When loading the anticancer agent doxorubicin thereinto, the nanocages showed higher anticancer effects than the same dose of PD-L1 antibody. Accordingly, the nanocages are expected as a next-generation drug that surmounts the limitation of immune checkpoint blocking therapy using antibodies.

The disclosure provides conjugates comprising a targeting moiety, e.g., an antibody, Fab fragment or single chain variable fragment (ScFv), and a lipid nanoparticle (LNP) encapsulating a therapeutic agent (i.e., payload), wherein the targeting moiety, e.g., antibody, Fab fragment or the ScFv, is conjugated to the lipid nanoparticle through a linker, and wherein the linker comprises an enzyme recognition sequence such as a sortase recognition motif or a lipoic acid acceptor peptide. The disclosure further provides methods of preparing such conjugates.

The present invention relates to multivalent and multispecific nanoparticle platforms and methods. A fusion protein comprising: a first nanocage monomer subunit of a nanocage monomer; and a bioactive moiety attached to the first nanocage monomeric subunit; wherein the fusion protein is self-assembled with a protein comprising a second nanocage monomer subunit to form a nanocage monomer.

The efficacy and indication of donanemab do not depend on the Fc region and are subject to transit across cell walls. They can be expanded by using their scFvs conjugated with N-methyl lobe of transferrin protein connected with an environment-sensitive cleavable linker to prevent exocytosis of the scFv yielding high exposure inside body cells such as in the brain, eye, and cancer cells that overexpress transferrin receptors.

The invention belongs to the technical field of microorganisms, and particularly relates to a method for expressing human lactoferrin by using lactococcus lactis. The method comprises the following steps: step 1, obtaining a codon-optimized hLF gene nucleotide sequence; 2, constructing a recombinant plasmid containing the hLF gene nucleotide sequence obtained in the step 1; and step 3, transferring the recombinant plasmid obtained in the step 2 into lactococcus lactis for induced expression. The heterologous expression of the human lactoferrin hLF is realized by utilizing the lactococcus lactis, the method is low in cost, convenient and fast, and a new way is provided for high-purity and high-yield preparation of the human lactoferrin hLF.

The invention relates to human lactoferrin for use in enhancing bone strength and / or bone growth in a subject.

The application discloses a kind of diflufenican hapten, antigen, antibody and its preparation method and application.The application prepares diflufenican hapten as shown in formula (I) and corresponding diflufenican antigen, and specific antibody for detecting diflufenican is prepared by diflufenican antigen, and further constructs the immune analysis method for directly detecting diflufenican pesticide residue, which is particularly suitable for on-site rapid detection, and can meet the needs of regulatory authorities and detection agencies formula (I).

This invention provides a side-chain coupled compound of a cell-binding molecule having a branched linker and an amanita toxin compound. [Solution] A side-chain conjugated compound of formula (I), TIFF2026097851000286.tif25170 In one embodiment, a side-chain conjugated compound is provided, in which T is a cell-binding agent / molecule, W is a C1-C18 extension unit, and D is an amanita toxin, or an isotope of a chemical element, or a pharmaceutically acceptable salt, hydrate, or hydrated salt; or a polymorphic crystal; or an optical isomer, racemate, diastereomer, or enantiomer thereof.

The invention discloses a fusion protein expression system suitable for expressing long-chain helper protein in yeast, which is a gene expression cassette of fusion protein of helper protein and bovine lactoferrin, and comprises a double KREAEA structural domain + flexible Linker tandem helper protein gene and bovine lactoferrin gene, and the fusion protein assists in folding of bovine lactoferrin in cells, so that the expression of long-chain helper protein is realized. The fusion protein is excised in cells, and the secretion efficiency of correctly folded bovine lactoferrin is remarkably enhanced.

The application relates to a detection method of oxicams for non-diagnostic purposes, and the application obtains a new oxicam hapten by optimizing the design of spatial configuration and chemical characteristics, and significantly improves the immunization efficiency of an antibody and the performance of an immunodetection device. The universal oxicam immunodetection device developed by the application integrates high sensitivity, wide detection range, anti-interference capability and rapid portability, overcomes the defects of the prior art, provides an efficient and reliable solution for rapid screening of oxicams in samples, and has significant technical progress and wide application prospect.

This invention belongs to the field of biotechnology, specifically relating to an osteogenic amino acid fragment Z01 and its screening and applications. This invention utilizes a unique cell screening platform specifically for Osx: the CL-Osx-EGFP cell line. This platform fuses Osx and EGFP, using EGFP as a tracking marker to directly reflect changes in Osx expression and screen for compounds that can activate Osx. Z01 was first discovered to effectively activate Osx, and its amino acid sequence is shown in SEQ ID NO.1. Pharmacokinetic and toxicological analyses were performed on Z01, and its osteogenic activity was verified in an ovariectomized rat osteoporosis model. Ultimately, it was demonstrated that Z01 possesses osteogenic activity, can improve bone microstructure, increase bone density, and has a wide range of applications.

This invention discloses a method and application for efficient synthesis of human lactoferrin through multi-copy integration, relating to the fields of genetic engineering and bioengineering. The invention provides a method for synthesizing human lactoferrin, including the steps of fermenting and culturing a recombinant Aspergillus niger strain, followed by isolation and purification to obtain human lactoferrin; the construction method of the recombinant Aspergillus niger strain includes the step of integrating the hLF gene into a gene locus in the host strain genome to construct the recombinant Aspergillus niger strain. This invention constructs a recombinant Aspergillus niger strain capable of recombinantly expressing human lactoferrin, initiating protein expression through a strongly inducible promoter, fusing endogenous high-secretion proteins, and optimizing the multi-copy integration method to integrate the lactoferrin expression cassette, achieving high-level synthesis of human lactoferrin, laying the foundation for the industrial production of lactoferrin or high-density fermentation of other food functional proteins using Aspergillus niger.

The invention relates to the technical field of biology, in particular to a recombinant pichia pastoris engineering bacterium, a construction method of the recombinant pichia pastoris engineering bacterium and application of the recombinant pichia pastoris engineering bacterium in secretory expression of ovotransferrin. The heterologous expression of ovotransferrin is effectively realized by optimizing ovotransferrin genes and utilizing molecular chaperone genes to strengthen the regulation and control capability of hosts, and meanwhile, by optimizing signal peptides and constructing high-copy recombinant pichia pastoris expression strains, the low-copy expression condition is verified and compared by utilizing fermentation expression, so that the heterologous expression of ovotransferrin is realized. According to the high-copy recombinant pichia pastoris engineering bacteria constructed by the invention, the ovotransferrin expression quantity is obviously improved and reaches 140 mg / L, the secretory expression efficiency of the ovotransferrin is effectively improved, and theoretical guidance is provided for heterologous expression and industrial production of the ovotransferrin.

In some aspects, the present invention provides chimeric transferrin receptor (TfR) polynucleotides and polypeptides. In other aspects, this invention provides chimeric TfR transgenic animal models and methods of using the animal models to identify therapeutics that can cross the blood-brain barrier.

Disclosed herein are engineered nucleases that bind and cleave a recognition sequence within intron 1 of a transferrin gene, and methods of using such engineered nucleases to produce a genetically-modified eukaryotic cell comprising a modified transferrin gene. Further provided are pharmaceutical compositions and methods for treatment of a variety of conditions through expression of a polypeptide of interest encoded by an exogenous nucleic acid molecule inserted in intron 1 of a transferrin gene and expressed under the control of the endogenous transferrin promoter.

The invention discloses a polypeptide module for promoting protein expression. The polypeptide module is polypeptide with an amino acid sequence as shown in SEQ ID NO: 2, wherein the polypeptide is formed by connecting a C end of a saccharomyces cerevisiae source signal peptide alpha-factor Pro section with two acidic residues EA; the composite signal peptide is formed by connecting a signal peptide OST1 from saccharomyces cerevisiae to the polypeptide module at the C end, the fusion expression of the composite signal peptide and the exogenous recombinant protein in saccharomycetes can improve the expression and secretion of the exogenous recombinant protein, and the composite signal peptide has popularization and application prospects.

The efficacy and indication of natalizumab do not depend on the Fc region and are subject to transit across cell walls. They can be expanded by using their scFvs conjugated with N-methyl lobe of transferrin protein connected with an environment-sensitive cleavable linker to prevent exocytosis of the scFv yielding high exposure inside body cells such as in the brain, eye, and cancer cells that overexpress transferrin receptors.