11 results about "P53 proteins" patented technology

The invention discloses a probe BBM for anchoring OPA1 protein and application of the probe BBM, and belongs to the technical field of biological analysis. Based on the characteristic that the OPA1 protein is rich in hydrophobic amino acid residues and polar amino acids, the probe BBM capable of generating multiple interaction forces with the OPA1 protein is designed by reasonably introducing hydrophobic groups and polar groups. Theoretical calculation and experimental results (including OPA1 knock-down and overexpression) show that the probe realizes efficient enrichment in a mitochondrial inner membrane region. By using the unique probe, the hydrogen peroxide induced mitochondrial inner membrane viscosity change is systematically researched, and the myocardial cell oxidative damage is further confirmed to be realized by a p53 protein mediated apoptosis pathway. The method provides a reliable means for accurately evaluating the oxidative stress of the mitochondrial inner membrane, and has important promotion significance for the development of the cardiovascular research field.

A method of obtaining cell derived vesicles comprising an active wild-type p53 is disclosed. The method comprising: (i) isolating cell derived vesicles from a biological sample comprising cells; and (ii) treating the cell derived vesicles with a DNA damaging agent, or the method comprising: (i) treating cells with a DNA damaging agent; and (ii) isolating cell derived vesicles from a biological sample comprising the cells. A proteinaceous preparation comprising cell derived vesicles and a pharmaceutical composition comprising the proteinaceous preparation are also disclosed. Methods of treating a disease, disorder or condition associated with a mutant or a nonfunctional p53 protein and methods of inducing apoptosis of a target cell comprising a mutant or a nonfunctional p53 protein are also disclosed.

The application discloses application of sulforaphane in preparation of an antienterovirus drug and belongs to the technical field of medicines, wherein the sulforaphane can inhibit the expression of viral proteins, inhibit viral genome replication and inhibit the production of virus particles to achieve the purpose of resisting enteroviruses; specifically, the sulforaphane can inhibit the replication of enteroviruses by up-regulating the content of p53 proteins. In addition, the sulforaphane can also be used for reducing the cell morphological damage caused by enteroviruses.

The invention discloses a compound for targeted enhancement of a transcription function of p53 protein and application of the compound. The compound TETACs not only can stabilize a p53 Y220C mutant protein, but also can actively recruit a transcription co-activator to a p53 target gene promoter region and specifically enhance the transcription function of p53, so that the cycle arrest and apoptosis of tumor cells are intensively induced, the tumor growth is effectively inhibited, and the compound TETACs has inhibitory activity on various tumor cells; in addition, as a heterobifunctional molecule, the TETACs play a role in a catalytic and substoichiometric manner, and have a more lasting curative effect and a wider therapeutic window.

Recently, aptamers have been considered in cancer diagnosis and treatment applications by binding to various bioreceptor molecules. Given that the p53 protein is responsible for approximately 50% of cancers, its identification is promising, but so far, no aptamer DNA sequence has been designed for the p53 protein and aptamer-based sensor. The purpose of this invention is to develop a nanoparticle-based aptamer sensor and use the p53 bioreceptor for cancer diagnosis with high sensitivity in the shortest time. In this regard, a DNA aptamer-based sensor was used on a glassy carbon electrode coated with gold nanoparticles / graphene oxide / conductive polymer . This sensor was created by the gold nanoparticles / aptamer-toluidine blue enhancer. The results obtained under optimal conditions of electrochemical investigation using amperometry indicated a detection limit of 0.29 picograms / mL in phosphate buffer and 0.341 picograms / mL in human blood plasma and a linear range of 1 to 300 picograms / mL for the sensor. This invention demonstrates the excellent and controllable performance of a modified carbon electrode to create a suitable sensor for detecting the cancer marker p53 protein.

The invention discloses a near-infrared AIE fluorescent probe based on a tetraphenylethylene-thiophene-indolium structure as well as a preparation method and application of the near-infrared AIE fluorescent probe. According to the preparation method, 5-(4-(1, 2, 2-triphenyl vinyl) phenyl) thiophene-2-formaldehyde (a reactant A) and 1-ethyl-2, 3, 3-trimethyl-3H-indolium iodide (a reactant B) are taken as raw materials, and the tetraphenyl ethylene-thiophene-indolium derivative (formula I) is prepared. The tetraphenylethylene-thiophene-indolium derivative has the characteristics of near infrared emission and aggregation-induced emission (AIE), can be used for real-time biological imaging and degradation of mutant p53 protein, and has a good application prospect in the aspect of developing tumor diagnosis and treatment integrated products.

Solutions to the problem of the invention are a method for selectively killing or removing a senescent cell, substance identification, and a method for purifying a senescent cell. Specifically, the invention includes an agent for removing a senescent cell, which is a drug for removing an in vivo senescent cell, the agent containing an inhibitor for glutaminase as an active ingredient, and a pharmaceutical composition containing the agent. The invention further includes a method for preparing a senescent cell, including the following steps (a) to (c): (a) synchronizing a cell with the G2 phase; (b) activating an intracellular p53 protein in the cell synchronized with the G2 phase; and (c) inhibiting polo-like kinase 1 (PLK1) activity in the cell treated in the step (b).

The present invention provides a dispiropyrrolidine derivative represented by the following formula (1), which has various substituents, inhibits interaction between Mdm2 protein and p53 protein and exhibits anti-tumor activity, wherein R1, R2, R3, ring A, and ring B in formula (1) respectively have the same meanings as defined in the specification.

The application provides a mouse fertilized ovum, wherein a sequence shown in SEQ ID NO. 1 in the fifth exon of a Trp53 gene is replaced by a fluorescent protein gene, and the individual developed from the fertilized ovum is a transgenic mouse for in-vivo labeling of p53 protein, and a construction method of the aforementioned fertilized ovum and transgenic mouse is provided. Through expression of the p53 and fluorescent label fusion protein, the application realizes accurate in-vivo labeling of the p53 protein, directly reflects the level of the p53 protein, and can track and analyze and sort abnormal cells by using flow cytometry according to the fluorescent protein label, so as to realize analysis and monitoring of tumor cell characteristics and tumor development process.

The application belongs to the technical field of biological medicine, and particularly relates to a polypeptide chimera targeting p53 protein stability and a preparation method and application thereof. The polypeptide chimera is a full polypeptide structure, which is connected by a USP7 recruiting domain, a p53 binding domain and a polypeptide linker containing an arginine chain, and has a general structure of A-L-B. The chimera can induce endogenous USP7 and p53 to be spatially adjacent as a molecular bridge, specifically removes the polyubiquitin chain of p53, up-regulates the p53 protein level in a concentration and time-dependent manner, prolongs the half-life of the p53 protein, activates the p21 downstream anticancer pathway, and the effect strictly depends on USP7. The chimera has high biological safety, is simple to synthesize, and provides a new strategy for the treatment of p53 function loss related tumors.

The invention relates to the technical field of nano-drugs, in particular to a difunctional nano-drug based on an autophagy targeting chimera-T cell connector as well as a preparation method and application of the difunctional nano-drug. The bifunctional nano-drug comprises a lipid shell, and an anti-CD3 antibody is coupled to the lipid shell; a T cell receptor targeting mutant p53 protein is inserted into the lipid shell; a medicine KPY is encapsulated in the lipid shell; and PFP is also encapsulated in the lipid shell. The nano-drug specifically recognizes a KRAS / TP53 mutant tumor through a surface-anchored T cell receptor, and low-intensity focused ultrasound is utilized to promote phase change of PFP to realize release of KPY at a tumor site so as to induce degradation of intracellular KRAS; and the CD3 antibody activates the CD8 + T cells to generate an extracellular immune activation effect. According to the technical scheme, the technical problem that in the prior art, targeted drugs for KRAS / TP53 co-mutation related tumors are lacked can be solved, and ideal application and popularization prospects are achieved.