152 results about "Humanin" patented technology

The present invention relates to novel Death Domain Containing Receptor-5 (DR5) proteins which are members of the tumor necrosis factor (TNF) receptor family, and have now been shown to bind TRAIL. In particular, isolated nucleic acid molecules are provided encoding the human DR5 proteins. DR5 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying antagonists and antagonists of DR5 activity. The invention also relates to the treatment of diseases associated with reduced or increased levels of apoptosis using antibodies specific for DR5, which maybe agonists and/or antagonists of DR5 activity.

The invention relates to the human protein FRAP, and in particular to the FKBP12-rapamycin binding domain thereof and to the ternary complex formed by the FRB domain, rapamycin and FKBP12. A new crystalline composition comprising the ternary complex, coordinates defining its three dimensional structure in atomic detail, and uses thereof are disclosed.

The invention discloses a human FGF21 mutant gene and a method for preparing a recombinant human FGF21 protein. The mutation is carried out on a human FGF21 gene, the base sequence after the mutation is as shown in SEQ IDNO.1, and the expression level of the gene after the mutation in prokaryocytes is significantly improved. The invention further provides a method for improving the expression level of the human FGF21 protein, which comprises the following steps: sequentially connecting a 6 multiplied by His tag gene, an SUMO tag gene, a hydroxylamine cleavage site gene and the human FGF21 mutant gene together, and then obtaining a gene as shown in SEQ ID NO.3; connecting the obtained gene with an expression vector, and obtaining a recombinant expression vector; transforming into host cells; culturing, inducing the expression of the recombinant protein, collecting and purifying the expressed protein, carrying out hydroxylamine cleavage, and further purifying. The method has the advantages of good specificity, high stability, capability of keeping the cleavage activity in a reaction environment system in a wide range, low preparation cost and the like.

The invention provides a preparation method for a soluble truncated human tumor necrosis factor-related apoptosis inducing ligand (TRAIL) active protein, comprising the following steps of: (A) designing and synthetizing an oligomerization deoxyribonucleic acid (DNA) single-stranded segment according to the amino acid sequence of the human TRAIL protein issued by a Genebank by the preference of a bacterium genetic code; (B) synthetizing a complete double stranded DNA by three-time polymerase chain reaction (PCR); (C) carrying out amplification by utilizing a T-carrier, and inserting the amplified double stranded DNA segment into an expression carrier and screening a positive transformant; (D) expressing the truncated human TRAIL protein in escherichia coli at low temperature; (E) purifying the protein by using a three-step method; and (F) determining the truncated TRAIL protein. The invention realizes that the truncated human TRAIL protein is efficiently expressed in an escherichia coli cell and a purification preparation technique thereof and overcomes the problem that an infusible inclusion body is easy to form in the prior art. The method has the advantages of simple operation, short fermentation time and easy purification, and moreover, the protein is ensured not to have any modification, and the protein reaches electrophoretically pure. The invention can be directly used for the research work of biochemistry and molecular biology and the oncology and the preclinical stage of tumor treatment or the development of clinical drugs.

The invention provides for SPARC polypeptides with a mutation corresponding to a deletion of the third glutamine in the mature form of the human SPARC protein, nucleic acids encoding such polypeptides, antibodies against such polypeptides, and methods of the use of such polypeptides, nucleic acids, and antibodies.

The invention provides a method of identifying an effective compound that modulates the binding of Humanin to Bax or Bid. The invention also provides a method of identifying an effective compound that modulates an activity of Bax or Bid. In addition, the invention provides a method of identifying a Humanin-like compound that binds to Bax or Bid or modulates an activity of Bax or Bid, or inhibits the apoptotic activity of Bax or Bid. The invention further provides an isolated polypeptide containing a mitochondrial-derived form of Humanin (SEQ ID NO:3) or a functional fragment thereof where the fragment contains the methionine at position 16 of SEQ ID NO:3.

The invention provides a construction method of a humanized IL15 gene modified non-human animal. A nucleotide sequence encoding a human protein IL15 is introduced into a genome of an animal by using ahomologous recombination mode, so as to construct a gene modified humanized animal. A body of the animal can normally express the human or humanized protein IL15, promote development of human T cellsand NK cells and can serve as an animal model for human IL15 signal mechanism researching and screening of drugs for diseases such as tumors, and thus, the animal has an important application value in research and development of new drugs for immunization target points.

The invention provides an anti-PD-L1/anti-LAG3 bispecific antibody, which can effectively block the interaction between PD-L1 and PD-1 and the interaction between LAG3 and a ligand (MHC II molecules,FGL1, etc.). The bispecific antibody is highly affinity to PD-L1 proteins (human PD-L1 protein, for example) and LAG3 proteins (human LAG3 protein, for example). The invention also provides an antibody and segment that has specificity on PD-L1 or LAG3 proteins; or an antibody and segment that has specificity on one or more other antigens.

The invention provides a construction method of an IL7R gene humanized modified animal model, a humanized IL7R protein, a humanized IL7R gene, a targeting vector of the IL7R gene and an application ofthe targeting vector in the field of biological medicines. A part of nucleotide sequences for coding the human IL7R protein are introduced into a non-human animal genome in a homologous recombinationmanner, and the animal model can normally express the humanized IL7R protein in vivo, and can be used for human IL7R signal mechanism research, tumor and immune related disease drug screening, and important application value is realized on the research and development of new drugs of immune targets.

A novel polypeptide having a cell death inhibitory activity and use thereof is provided. The polypeptide and the polynucleotide encoding it can be used as a diagnostic, therapeutic or prophylactic agent for various diseases and disorders. Certain suitable diseases and disorders which may be diagnosed, treated, or prevented with the polypeptide and the polynucleotide encoding it are selected from neurodegenerative diseases, brain dysfunctions, cancers, immunological disease, infections, gastrointestinal diseases, circulatory diseases, and endocrine diseases. The polypeptide and the polynucleotide encoding it can be used as a cell death inhibitor.

The invention discloses a method for preparing human LIGHT-Fc fusion protein by using a pichia expression system, comprising the following steps of: (1) constructing recombinant expression plasmid pPIC9K-LIGHT-Fc; (2) preparing and screening expression human LIGHT-Fc fusion protein yeast engineering bacteria; and (3) expressing and evaluating the human LIGHT-Fc fusion protein in pichia. The invention makes up the deficiency of the traditional human LIGHT preparation method and the expression mode of a prokaryotic expression system, otherwise, if being used for producing industrial human LIGHT protein, the invention has the advantages of simple operation, short growth cycle of raw organisms, large production scale (capable of carrying out high-density fermentation), low extraction cost, high activity of products, and the like and has important industrial application prospect and actual significance.

The present invention is based on the discovery that Humanin and humanin analogues protect pancreatic beta cells in vitro and in vivo from apoptosis. Accordingly, humanin and its analogues are useful for preventing and treating diabetes and promoting beta cell survival in a number of applications.

The invention relates to a genetically-modified non-human animal and application thereof, in particular to a transgenic mouse model and application thereof in the aspect of screening of a targeted medicine. According to the transgenic mouse model and application thereof in the aspect of screening of the targeted medicine, by targetedly knocking out and replacing a mouse protein C gene by means ofa human protein C gene expression cassette, a humanized protein C knock-in mouse is generated. The mouse has fertility, and can hybridize with another mouse disease model (such as a mouse in the deficiency of a blood coagulation factor VIII or a blood coagulation factor IX) to produce a humanized protein C mouse disease model (such as a humanized protein C factor VIII-deficient mouse model or a humanized protein C factor IX-deficient mouse model). The mouse model can be used for studying functions in vivo of human protein C and human activated protein C (APC). The mouse model is the first mouse model used for testing a therapeutic candidate medicine, which targets the human protein C or the APC, in vivo, and has very high economic value and scientific research value.

Naturally-occurring variants of human Rgr oncogene protein, in particular, abnormally truncated variants found in T cell malignancies, as well as the human Rgr protein are encompassed by the present invention. Also included are antibodies thereto and nucleic acid molecules encoding human Rgr protein and naturally-occurring variants thereof. The present invention further provides methods for diagnosing and treating T cell malignancies associated with abnormally truncated transcripts of human rgr oncogene and/or abnormal truncation of human Rgr protein.

The invention provides a construction method and application of a thrombopoietin (THPO) gene humanized non-human animal. The method comprises the following steps: introducing a sequence for encoding human THPO protein into an animal genome by using a homologous recombination manner; the animal can normally express the human or humanized THPO protein in vivo, to promote the development of human T cells and NK cells; the non-human animal can be used as an animal model for human THPO signal mechanism research and drug screening for diseases including tumors and the like, and has important application value for new drug research and development of immune targets. The invention further provides a targeting vector of a THPO gene, sgRNA of the target THPO gene and application of the targeting vector and the sgRNA to preparation of a humanized THPO gene.

The invention discloses a stress phosphorylation antibody aiming at a human Tudor-SN protein T103 site and a preparation method thereof. The preparation method adopts a multifunctional human Tudor-SN protein as a research object and comprises the following steps of determining if threonine at a 103 site of a human Tudor-SN protein under external environment oxidation stress is subjected to phosphorylation modification by near-infrared double-color laser imaging and mass spectrometry, synthesizing a T103 phosphorylation site-containing semiantigen polypeptide according to the secondary structure prediction result, coupling the T103 phosphorylation site-containing semiantigen polypeptide and a carrier protein (KLH) into a complete antigen, carrying out immunization on SPF-level New Zealand white rabbit by the complete antigen combined with an adjuvant four times and collecting, purifying and identifying a T103 specific stress phosphorylation polyclonal antibody. In practical application, Tudor-SN protein epigenetic phosphorylation modification in different stress environments can be detected, the effect mechanism of the Tudor-SN protein epigenetic phosphorylation modification in cell stress tumor propagation and migration can be discussed and a latent action target point for clinical tumor disease diagnosis and treatment is provided.

The invention discloses an allophycocyanin (APC) and Annexin V protein coupling method. The APC and Annexin V protein coupling method comprises the following steps: 1, an Annexin V protein is expressed and purified: specifically, 1.1, a gene sequence is optimized, specifically the gene sequence of the human Annexin V protein is looked up, the human Annexin V gene sequence is optimized, a termination codon sequence is removed, the human Annexin V gene sequence is connected into a prokaryotic expression vector, front and back His tag proteins are retained, and preparation is made for protein purification and subsequent coupled fluorescein purification; and 1.2, the Annexin V protein is subjected to inducible expression, specifically, a recombinant plasmid single colony is picked and inoculated into an LB liquid culture medium containing kanamycin, and culturing is conducted until the concentration OD600 of bacterial liquid is 0.4-0.6, and an inducer is added into the bacterial liquid forinduction culture. When the Annexin V gene sequence is designed, His tags at the two ends of the protein are reserved, the Annexin V protein and an Annexin V-APC conjugate are convenient to purify, only conventional nickel column purification is needed, special purification equipment is not needed, the purification steps are few, the purification time is short, the purification cost is lowered, the good biological activity of the protein is maintained, and the Annexin V protein can be used for cell apoptosis detection.

Provided herein are compositions, methods and uses of humanin or a humanin analog, for example, in treating a subject with humanin or a humanin analog, in part, to protect white blood cells from suppression or cell death induced by an autoimmune, anti-tumor or anti-cancer therapeutic agent.

The present invention is directed to methods and compositions for preventing or reducing atherosclerotic lesions and plaques. Specifically, the instant invention provides methods for using humanin and its analogues to prevent or reduce the formation of atherosclerotic plaques. Also provided are methods of using humanin and its analogues to improve the survival of endothelial cells, particularly aortic endothelial cells.

The invention provides a high expression and production method of recombinant human thrombin in animal cells. Specifically, the invention provides a fusion gene and a fusion protein coded by the same. The gene contains signal peptide sequence of human protein C and Gla structural domain deleted human prothrombin gene sequence, and can enhance expression level of human prothrombin-2. The invention also discloses a method for employing a recombinant expression vector containing the above nucleotide sequence to express and produce human prothrombin in animal cells. The invention also discloses a method for producing recombinant human thrombin by purification and activation. The recombinant human thrombin produced by the invention has biological activity satisfying treatment of correlative clinic diseases.

The invention provides a construction method of an IL1R1 gene-humanized modified non-human animal, a humanized IL1R1 protein, a humanized IL1R1 gene, a targeting vector of the IL1R1 gene and application of the targeting vector in the field of biological medicine. By utilizing a homologous recombination manner, a part of nucleotide sequences for encoding human IL1R1 protein are introduced into a non-human animal genome. The humanized IL1R1 protein can be normally expressed in a non-human animal body, and the non-human animal can be used for researching a human IL1R1 signal mechanism and screening drugs for cardiovascular diseases, autoimmune diseases, infectious diseases, degenerative diseases, sleep diseases, tumors or inflammation-related diseases, and has important application value forresearch and development of new drugs of immune targets.

By using a G protein-coupled receptor protein containing an amino acid sequence, which is the same or the substantially the same as an amino acid sequence represented by SEQ ID NO:1, SEQ ID NO:10, SEQ ID NO:12 or SEQ ID NO:14, or its salt together with humanin, a compound or its salt capable of changing the binding properties of the above receptor protein or its salt to humanin can be efficiently screened.