65 results about "Cell penetration" patented technology

The application belongs to the field of medicine, and particularly relates to a cell penetrating peptide Phage-Dec and application thereof in antibiosis. The cell penetrating peptide Phage-Dec has excellent cell penetration ability and antibacterial activity, can effectively penetrate the cell membrane, target and inhibit bacterial growth, and thus achieves the purpose of antibiosis. Research shows that Phage-Dec has a significant inhibitory effect on various pathogenic bacteria, and can effectively reduce the reproduction speed of bacteria. The use of the cell penetrating peptide provides a new idea for antibacterial treatment, has a good clinical application prospect, and lays a solid foundation for developing a new antibacterial drug based on a bacteriophage source.

The invention discloses a methotrexate-cationic polypeptide conjugate as well as a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. According to the conjugate, MTX and cationic polypeptide with the amino acid sequence shown as SEQ ID NO: 1 are connected through chemical bonding, the membrane binding characteristic of oligomeric lysine and the transmembrane capacity of TAT cell-penetrating peptide are creatively fused, and a polypeptide carrier system with efficient cell penetrating capacity is constructed; mTX obtains amphipathy and electropositivity through peptide fragment modification, stable nanoparticles can be spontaneously formed, and the problems of poor water solubility and instable acidity of raw material medicines are effectively improved; according to the conjugate, the accumulation efficiency of the medicine at a diseased region is remarkably improved by utilizing the targeting characteristic of the polypeptide carrier, the action time of the medicine is prolonged through a precise delivery mechanism, and meanwhile, the system toxicity is reduced. The preparation method adopts mild coupling reaction conditions, and the product is high in purity and excellent in stability; the compound is suitable for treating immune-mediated inflammatory diseases and specific malignant tumors, and provides an innovative solution thought for treating related diseases.

The application discloses a stapled peptide compound for selectively degrading MYC protein, a preparation method and application thereof; the compound is sequentially connected in the N-terminal to C-terminal direction by a peptide recognition segment, a flexible linker and a chaperone-mediated autophagy recognition motif KFERQ or a similar motif; the peptide recognition segment is introduced by an (i, i+7) site alkenyl amino acid and a Grubbs catalytic RCM reaction to form a full carbon hydrogen stapling bridge to stabilize the alpha-helix conformation; stapled modification of a typical compound MAX-7 significantly improves the alpha-helix content, the protease stability and the cell penetration, so that the compound can efficiently enter cells and be located in lysosomes, and MYC protein is selectively degraded through the CMA pathway; in-vitro experiments show that MAX-7 can inhibit the proliferation, migration and invasion of various MYC-driven tumor cells, and induce apoptosis; the application provides a brand-new lysosome-directed degradation strategy for the "undruggable" target MYC, and establishes a universal technical platform which can be popularized to other difficult drug proteins.

The invention relates to the technical field of biological medicines, and provides a polypeptide targeting a BRAF dimer and an application of the polypeptide in tumor resistance, the polypeptide takes a straight-chain peptide TRHVNILLFM-OH as a peptide chain template, the straight-chain peptide is constructed through specific amino acid replacement, the C terminal is gradually truncated and cyclized to construct a cyclic peptide, and a specific sequence is coupled to develop a composite peptide strategy for modification, so that the polypeptide targeting the BRAF dimer is obtained. The cyclic peptide CBF-2, the cyclic peptide CBF-2-2 and the cyclic peptide SCBF-2-2 are obtained. Experiments prove that the polypeptide can effectively inhibit proliferation and invasion of tumor cells; the serum protein has high stability and excellent cell penetrating capability, and can penetrate through a cell membrane to enter cytoplasm, so that target protein in cells can be better targeted to exert biological functions of the target protein. Therefore, the multi-functional composite peptide can be developed through a polypeptide modification strategy, the membrane permeability and the stability of the multi-functional composite peptide are improved, the binding force of the multi-functional composite peptide and the BRAF protein is further improved, and the effects of inhibiting proliferation of tumor cells and resisting invasion are achieved at the same time.

The invention provides a p53 fusion protein based on a targeted colorectal cancer marker CEA and application of the p53 fusion protein in preparation of medicines for inhibiting colorectal cancer, and relates to the field of biological medicines. The fusion protein comprises any one of the following components: p28-p53, MBP-TEV-p14ARF (1-63)-linker-p28, p28-p53-CEABP1, CEABP1-p28-p53, and CEABP2-p28-p53, and the fusion protein comprises any one component selected from the group consisting of the following components: a protein A, a protein B, a protein A, a protein B, a protein C and a protein B, according to the application, p53 and p14 ARF proteins for inhibiting cell proliferation in a human body, cell-penetrating peptide and designed protein CEABP1 or CEABP2 of a targeted binding colorectal cancer marker CEA are fused for the first time, and cell experiments and mouse experiments prove that the protein has a relatively high function of inhibiting growth of colorectal cancer cells, does not influence normal cell growth and has a wide application value.

The application belongs to the technical field of biological medicine, and particularly relates to preparation and application of a self-assembled nanocomposite based on a CRISPR / Cas9 system and ursolic acid. The nanocomposite takes UA self-assembled nanodrug UA NPs as a core, and is co-assembled with low-molecular-weight protamine LMWP having good cell penetration capacity and a CRISPR / Cas9 plasmid pTIM3 for knocking down TIM3 to form a nanocomposite ULP NPs. The nanocomposite prepared in the application can be enriched at a tumor site through EPR effect, and can reach the effect of enhancing liver cancer immunotherapy by knocking down the inhibitory immune checkpoint TIM3. The regulation characteristics and molecular mechanism of the UA NPs as a self-assembled general template for delivering the CRISPR / Cas9 system to inhibit the immune checkpoint TIM3 are disclosed, and the application has a wide application prospect in liver cancer immunotherapy.

The present application relates to the technical field of genetic engineering, and specifically discloses a Chlamydomonas reinhardtii SnRK2.7 gene and application thereof in adaptation to osmotic stress and maintenance of cell survival. The present application first discloses SnRK2.7 the key biological function of the gene in maintaining Chlamydomonas cell homeostasis. By knocking out the gene through CRISPR / Cas9 gene editing technology and adopting an expression frame driven by an endogenous promoter for genetic back complementation, it is confirmed that SnRK2.7 the gene positively regulates cell osmotic stress tolerance and maintains cell long-term survival. In addition, the present application first discovers that the SnRK2.7 protein is specifically located in the Chlamydomonas expansion vesicle, which provides direct spatial evidence for the cell function. The above discovery not only expands the understanding of the osmotic stress signal transduction mechanism of Chlamydomonas, but also provides a new gene target and research tool for the improvement of microalgae stress adaptability, and has important basic research value and biological technology application potential.

The Applicant has discovered that the peptide of SEQUENCE ID NO: 1 (WKDEAGKPLVK) mediates changes in key biomarker activities associated with NASH (Table 1), and that the peptide is capable of penetrating HepG2 liver cells in a hepatic cell penetration assay (FIG. 1). In addition, the Applicant demonstrates that treatment with pep_260 (SEQ ID 1) for 44 days significantly relieves macro-vesicular steatosis in obese diabetic KKAy mice (FIG. 2) In a first aspect, the invention relates to the use of a peptide comprising SEQUENCE ID NO: 1, or a functional (or therapeutically effective) variant or functional fragment of SEQUENCE ID NO: 1 (hereafter “peptide active agent” or “peptide of the invention”), in a method for the treatment or prevention of non-alcoholic fatty liver disease (NAFLD), in particular non-alcoholic steatohepatitis (NASH), in a mammal.

An L-form ribonucleic acid (L-RNA) aptamer-antisense oligonucleotide (ASO) conjugate comprise the L-RNA aptamer, which comprises a ribonucleic acid sequence. The ASO comprises a deoxyribonucleic acid sequence selected from a group. A method of imaging amyloid precursor protein (APP) rG4 in a cell comprising transfecting the cell with a messenger RNA of APP, permeating the cell, contacting the permeated cell with a cyanine3 (Cy3) labeled APP nucleic acid probe and the L-RNA aptamer-ASO conjugate, and subjecting the product to fluorescence microscopy analysis to produce an image of the APP rG4 in the cell.

The utility model discloses a brine blending device for a red blood cell osmotic brittleness test. The brine blending device comprises a main shell and a position mark sensing unit, a salt water blending unit and a center alignment unit; a master controller; a to-be-loaded test tube group is placed on the bottom placing table, the center alignment unit is used for placing the to-be-loaded test tube group in the middle position, the position mark sensing unit is used for measuring and calculating the distance between the head test tube and the tail test tube of the test tube group so as to guide the horizontal moving unit to rapidly move to the position over the test tubes relative to the center of the device, and the visual camera and the injection angle adjusting assembly are used for adjusting the injection angle. The injection head is aligned with a test tube opening, and the metering pump is started to inject saline water and distilled water into the test tube according to a fixed proportion. Based on a saline water filling mode of mobile hovering injection, a horizontal moving unit is arranged to realize movement of an injection head above a test tube group, so that the problem of material resource waste caused by a traditional one-tube one-path scheme is solved; in addition, by arranging a visual camera and an ejection angle adjusting assembly, the technical risk that saline water is injected out of the test tube is avoided to a great extent.

The use of a cell-permeant molecular probe to assay the presence, and monitor the production, of the reactive oxygen species, superoxide, in red blood cells (RBCs) is described. The assay is performed using electron paramagnetic resonance (EPR) spectroscopy and a cell-permeant hydroxylamine spin trap. The cell-permeant molecular probe is not detected or quantifiable by EPR in its reduced form. However, upon entering the RBCs, the probe is oxidized by reacting with superoxide to yield a stable nitroxide radical that is detected and quantified using EPR. Our studies indicate that superoxide production is consistent with RBC metabolism that predicts lipid oxidation, membrane injury and poor post-transfusion performance. Therefore, measurement of reactive oxygen species can be used as an indicator of RBC quality at the time of donation and after storage.

The invention provides a gH625-H2A histone as well as chromatin and application thereof. The histone is prepared by adding peptide gH625 into histone H2A; the application comprises the application of the gH625-H2A histone and the chromatin thereof in preparation of drugs or drug delivery systems and the application of the gH625-H2A histone and the chromatin thereof in preparation of skin care products and cosmetics. The invention provides the gH625-H2A histone and the chromatin thereof, the histone and the chromatin have strong cell penetration and skin permeation effects, the histone and the chromatin are expected to promote the development of a transdermal gene delivery system and biological medicines and skin care products, and the prepared biological medicines and the skin care products have the advantages that the development of the transdermal gene delivery system and the biological medicines and the skin care products is facilitated; passive skin delivery of nucleic acids, small peptides, growth factors and enzymes is achieved without physical or chemical intervention.

The application belongs to the technical field of biological medicine, and particularly relates to a cell penetration inhibitory peptide and application thereof in breast cancer. Specifically, aiming at the interaction between circHIF-1alpha (11, 12) and IGF2BP2, a novel compound named cell penetration IGF2BP2 inhibitory peptide (IIP) is designed to intervene, so as to inhibit the energy metabolism re-regulation and tumor progression of breast cancer. The application first discloses a new use of IIP as an inhibitor of circHIF-1alpha (11, 12). In-vitro experiments prove that IIP can significantly inhibit the energy metabolism reprogramming and tumor progression of breast cancer cells. In summary, the application provides an innovative breast cancer treatment method based on the interaction between circRNA and protein, and successfully intervenes the disease process of breast cancer through the design and application of IIP, which opens up a new direction and possibility for the development of breast cancer treatment.

The application belongs to the technical field of fluorescent probe, and particularly relates to a non-oxygen-dependent multi-mode selenium rhodamine-based photodynamic photosensitizer as well as preparation and application. In order to develop a non-oxygen-dependent and efficient photosensitizer, based on the selenium rhodamine spiro ring 'on-off' mechanism, a N-nitroso functionalized selenium rhodamine photosensitizer SeR-NO is developed, which exists in the form of lactone with closed ring in PBS, has very small cell dark toxicity and excellent cell permeability; under light, the photosensitizer can not only produce a large amount of ROS through type I and type II mechanism, but also can catalyze NADPH oxidation and Cyt c reduction in an oxygen-independent manner, therefore, SeR-NO has large phototoxicity, and can induce cell death through ferroptosis in normoxia (21% O2) and hypoxia (2% O2).

The invention discloses a CD3 antibody-polypeptide, which is characterized in that an amino acid sequence of a light chain variable region of a CD3 antibody is linked with an amino acid sequence of polypeptide through a triple link of a GGGGS flexible joint; and the CD3 antibody-polypeptide can be coupled with the RNP compound through a chemical bond to form the CD3 antibody-polypeptide-RNP compound. The CD3 antibody-polypeptide-RNP compound is used as a delivery system for gene editing in the TILs cells, in the gene editing process, CD3 antibody-polypeptide has good cell penetrability and stability, an exogenous gene can be efficiently and accurately delivered into a double-chain incision manufactured on a TRAC gene of the TILs cells, cell damage caused by electrotransfection is avoided, and the CD3 antibody-polypeptide-RNP compound can be applied to gene editing of the TILs cells. The prepared TI Ls cells have a higher proportion of memory T cells (CD45RO < + > CD62L < + >) and a higher proportion of tumor specific T cells (CD8 < + >), so that the TI Ls cells have a better tumor killing effect.

The present application relates to a kind of new cell penetrating peptides and its use. It is proved that the 12 cell penetrating peptides of the present application have excellent cell penetration ability and mass transfer effect in vitro and in vivo, since the above-mentioned cell penetrating peptides can effectively deliver biologically active substances to cells, tissues and other in vivo, and are expected to be widely used in research fields, various disease diagnosis and treatment fields, etc.

Described is an antibody-drug conjugate (ADC) having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable, preferably a camptothecin cytotoxic molecule which is cell-permeable; and as a second payload a topoisomerase I inhibitor which is not cell-permeable, preferably a camptothecin cytotoxic molecule which is not cell-permeable. Moreover, described is a pharmaceutical composition comprising said ADC and at least one pharmaceutically acceptable ingredient. Further, described is an ADC for use in a method of treating a patient suffering from, being at risk of developing, and / or being diagnosed for a neoplastic disease.

The invention belongs to the technical field of traditional Chinese medicine extraction, and particularly relates to an extraction method of a high-activity ginseng extract, which is used for improving the conversion and extraction efficiency of rare ginsenoside Rg1, Rg3, Rg5, Rh2 and Compound K. The extraction method combines microbial fermentation, electrostatic field wall breaking and supercritical CO2 extraction, the high-voltage pulse electric field induces ginseng cells to generate an electroporation effect, permeability of cell membranes and cell walls is improved, supercritical CO2 extraction has high cell permeability, the extraction rate and purity of ginsenoside are improved, and in addition, a catalytic promoter added in the extraction process is beneficial to conversion catalysis of rare ginsenoside components.

The present application relates to the field of biological medicine, and particularly relates to a recombinant fusion protein for targeted treatment of tumors and a preparation method thereof.The present application combines the protein transduction domain TAT with GLIPR1 to form a fusion protein to improve the targeting and penetration ability of GLIPR1 and optimize the defect that GLIPR1 protein mainly enters the cytoplasm by endocytosis.The recombinant fusion protein TAT-GLIPR1 prepared by the present application has significantly enhanced cell penetration ability compared with GLIPR1 protein, and improves the efficiency of GLIPR1 into tumor cells.The drug use concentration can be significantly reduced, and the drug side effects can be reduced;compared with traditional gene therapy, the problems of possible toxicity and immunogenicity can be avoided, and the recombinant fusion protein can be used as a drug for targeted treatment of tumors, and provides important technical support for the application of GLIPR1 targeted treatment of tumors.

The invention belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to an osteoarthritis targeted traditional Chinese medicine nano preparation and a preparation method thereof.The traditional Chinese medicine nano preparation is prepared from, by weight, 15-25 parts of traditional Chinese medicine extract, 4-8 parts of functional peptide, 3 parts of nano zinc oxide, 12-15 parts of coupling agent, 10 parts of modifier, 30-48 parts of phospholipid and 14 parts of cholesterol; the traditional Chinese medicine extract obtained through toxicity attenuation and purification contains rich terpenoids, flavones, saponins and other micromolecular anti-inflammatory immune regulation active substances, multi-target treatment of arthritis is provided, the designed functional polypeptide has inflammation specific response and cell penetrating capacity, focus enrichment of treatment components is achieved, and the treatment effect is good. The toxicity to normal tissues is reduced while the curative effect is improved.

The invention discloses application of intestinal flora metabolite reuterin in preparation of a medicine for relieving or treating atherosclerosis, and relates to the technical field of medicine. The reuterin can reduce the blood sugar level, the total cholesterol level and the low-density lipoprotein cholesterol level, reduce liver lipid deposition, improve liver fatty degeneration, promote growth of beneficial bacteria, inhibit proliferation of potential harmful bacteria and inhibit cell penetration and uptake of low-density lipoprotein in endothelial cells. According to the application, the fact that the reuterin can be used for relieving or treating the atherosclerosis is disclosed for the first time, a new direction is provided for treating the atherosclerosis, and experiments show that the reuterin does not cause adverse effects on liver and kidney functions of mice after being used for a long time, and shows that the reuterin has good biological safety.

Compounds having the structure (3) as shown in the specification wherein Y is as defined in the specification and wherein: [R2bR2a] represents a reaction product between R2b and R2a of Formulas (2) and (1), respectively, R3 functions as a cell penetration moiety, and R1 functions as a binding moiety to bind to the payload (P) to form a conjugate with P, wherein R1, R3, A, D, L1, L2, L3, L4, L5, L6, L7, r, m, s, n, p, and q are as defined in further detail elsewhere in this disclosure. Also described herein are methods of producing compounds of Formulas (1), (2), and (3), conjugates thereof with a payload (P), pharmaceutical compositions thereof, methods of delivering the conjugates to subjects or cells, and methods of treating a disease or condition by administering such conjugates.

Formulas for use in enhancing the transduction efficiency of lentiviral vector (LV) particles into various target cells are disclosed herein. For example, a formulation for use in enhancing the transduction of paramyxovirus pseudotype lentiviral vector particles into target cells may comprise a cell-permeable peptide (CPP) comprising at least one of Vectofusion-1 or LAH4-C; and poloxamer 407, wherein the concentration of poloxamer 407 is greater than or equal to the concentration of CPP. Additionally, a method of using such formulations to enhance the transduction of LV particles, including particularly in vivo transduction, is disclosed herein.

The invention discloses a polypeptide coupling compound as well as a preparation method and application thereof, and relates to the technical field of polypeptides. The structure of the polypeptide coupling compound is shown in the specification, and the Peptide is any one polypeptide sequence as shown in SEQ ID NO. 1 to 38. The resorcinol compound is coupled with the polypeptide sequence, so that the water solubility of the resorcinol derivative is remarkably improved, the cell penetrability and the skin permeability are improved, the effective transfer of the resorcinol derivative in the skin is promoted, and meanwhile, the skin beautifying effect of polypeptide and the whitening activity of the resorcinol derivative are fused; and multiple effects of whitening, wrinkle resistance and aging resistance are realized. The polypeptide coupling compound provided by the invention is simple in structure, mild in reaction condition, easy to prepare, high in synthesis success rate and relatively high in product purity, and has a good market prospect when being applied to whitening cosmetics.

This invention provides the application of the ASPL-TFE3 fusion gene in the preparation of drugs that enhance the efficacy of immune checkpoint inhibitors. The nucleotide sequence of the fusion gene is shown in SEQ ID NO:1 or SEQ ID NO:2. This invention relates to the field of tumor immunotherapy. This invention utilizes the ASPL-TFE3 fusion protein to regulate TFE3 expression and activity to enhance tumor cell autophagy and immune cell penetration, thereby improving the efficacy of immune checkpoint inhibitors in treating tumors.

The invention discloses a composition for delaying senescence and keeping skin young, the composition comprises three active components of PQQ, ergothioneine and NAD +, the mass ratio of PQQ to ergothioneine to NAD + is 1: 1: 1, the PQQ is used for protecting mitochondrial functions and promoting generation of new mitochondria; according to the ergothioneine, telomere shortening is delayed through an OCTN1 transporter mediated cell penetration mechanism; nAD + is used for activating a Sirtuins protein family and repairing DNA damage, the invention relates to the technical field of medicine, PQQ is delivered in a targeted manner through lipid nanoparticles, accurately acts on mitochondria, resists attack of 95% or more of free radicals, promotes generation of new mitochondria and delays cell aging from an energy source, high-purity ergothioneine penetrates through a cell membrane through OCTN1 transporter protein, and the effect of repairing DNA damage is achieved. The NAD < + > directly activates Sirtuins family proteins, the DNA damage repairing efficiency is improved by 60%, the skin collagen density and myocardial cell viability are remarkably improved, and physiological age signs are reversed.

The present application relates to the field of biological materials, in particular to a high-efficiency transdermal recombinant humanized elastin as well as a preparation method and application thereof. In view of the problem that macromolecular drugs and proteins are difficult to be effectively absorbed through skin in the prior art, the present application discloses a high-efficiency transdermal recombinant humanized elastin, a coding gene, a recombinant vector, a recombinant genetically engineered bacterium, and a preparation method and application thereof. The protein has cell penetration ability and transdermal ability, and is obtained by protease cleavage from a precursor elastin. The nucleotide sequence of the coding gene of the precursor elastin is a sequence shown in SEQ ID NO. 3 or an equivalent sequence. The recombinant humanized elastin of the present application can be applied to skin care products, dressings, implants, artificial skin, artificial blood vessels, medical devices, biological materials or functional foods, and is particularly suitable for external preparations for anti-wrinkle, anti-aging or skin barrier repair.

The present application belongs to the field of polypeptide drug preparation, and particularly relates to a kind of short peptide dimer and its nanocomposite.The tripeptide (Ser-Cys-Arg) is assembled to form short peptide dimer by hydrogen bond in aqueous solution, which first discloses that short peptide forms cyclic dimer structure through intermolecular hydrogen bond, without using chemical crosslinking agent, oxidizing agent or protection / deprotection step, and the process is more simple and mild, and more suitable for synergistic assembly with drug molecules to form nanocomposite.The short peptide dimer provided by the present application can efficiently encapsulate model drugs to form "peptide-drug" nanocomposite, which can diffuse in gel matrix to epidermis, form multiple non-covalent interactions with skin lipids and keratin, significantly improve the transdermal permeability of drugs through dual pathways of cell penetration and intercellular gap transport, and reach the action site to realize efficient targeted drug release.

The present invention relates to a peptide having a cell penetration ability and a strong mitochondrial targeting property at a low concentration, and a medical use thereof. A peptide or a dimer thereof, of the present invention, is very useful in the prevention or treatment of diseases accompanied by mitochondrial dysfunction, and liver diseases.

The invention discloses application of a composite biological material in hernia repair surgery, and belongs to the technical field of biotechnology, the composite biological material comprises a nanofiber scaffold, the scaffold is prepared by compounding polylactic acid-glycolic acid and silk fibroin, the weight ratio of the polylactic acid-glycolic acid to the silk fibroin is 70: 30, and the weight ratio of the polylactic acid-glycolic acid to the silk fibroin is 20: 30. The nanofiber scaffold is prepared through an electrostatic spinning technology and is used for providing mechanical support and promoting cell attachment and proliferation; the fiber is of a porous structure, the pore size is 10-100 microns, and cell permeation and nutrient substance exchange are facilitated; the polylactic acid-glycolic acid / silk fibroin composite scaffold is prepared by compounding polylactic acid-glycolic acid and silk fibroin, the mechanical properties of natural tissues are simulated, and a good growth scaffold is provided for cells. The gel layer is prepared through a solution phase separation method, and provides additional biological activity support and a cell attachment surface for the nanofiber scaffold. By arranging the antibacterial coating, the risk of postoperative infection is reduced, and meanwhile, protection is provided for materials and human tissues.