39 results about "Enzyme degradation" patented technology

Disclosed are Hematopoietic Progenitor Kinase 1 (HPK1) degradation / disruption compounds including a HPK1 ligand, a degradation / disruption tag and a linker, and methods for use of such compounds in the treatment of HPK1-mediated diseases.

The invention discloses an implantable acellular matrix material and a preparation method thereof, and belongs to the field of biomedical materials. According to the method, natural animal tissues (such as pericardium, achilles tendon or small intestine submucosa) are used as raw materials, a low-temperature chemical combined decellularization treatment technology is adopted, and the method comprises the multi-step synergistic process of pre-cooling soaking balancing, low-temperature enzymolysis, low-concentration surfactant gradient permeation cleaning, low-temperature nuclease degradation, non-crosslinking sterilization and the like. Under the condition that the treatment temperature is strictly kept at 0-8 DEG C, cell components and genetic materials (the residual DNA content is 1t, and the dry weight is 8 ng / mg) are efficiently removed, and meanwhile the natural three-dimensional fine structure of an extracellular matrix (ECM), the integrity of collagen fibrils and key bioactive components (such as glycosaminoglycans (GAGs)) are reserved to the maximum extent. The host immunological rejection reaction of the obtained material is remarkably reduced, host cell ingrowth, vascularization and tissue function reconstruction can be effectively promoted after implantation, and the material is suitable for high-end implantation scenes such as soft tissue repair and regenerative medical stents.

Provided is a fusion protein, the fusion protein containing a GLP-1 polypeptide and an immunoglobulin Fc domain, wherein the GLP-1 polypeptide is covalently linked to the immunoglobulin Fc domain, the GLP-1 polypeptide is selected from human GLP-1(9-37) and human GLP-1(9-36) amides, and the GLP-1 polypeptide contains G22E and / or R36G substitutions relative to a natural human GLP-1 polypeptide. The human GLP-1(9-37) and human GLP-1(9-36) amides are products respectively resulting from losing two amino acids at the N-terminus of natural human GLP-1(7-37) and human GLP-1(7-36, by means of DPP4 enzyme degradation, and were previously considered as biologically inactive fragments. Provided are a polynucleotide encoding the fusion protein, a vector and cell containing the polynucleotide, and the use thereof, for example, in the preparation of drugs for treating metabolic diseases related to lipid metabolism disorders, complications of metabolic diseases, neurodegenerative diseases and other related diseases.

The invention discloses synthesis of 5-nucleotide phosphorodithioamide and application of the 5-nucleotide phosphorodithioamide in oligonucleotide. The oligonucleotide modified by the phosphorodithioamide comprises nucleotide structural units shown in a formula I or a formula II,..., the formula I,..., the formula II. According to the invention, through specific limitation of the structure of a nucleotide dithiophosphoramide monomer, the prepared oligonucleotide comprises a 5-nucleotide dithiophosphoramide structural unit. Compared with a traditional oligonucleotide molecule, the oligonucleotide molecule modified by nucleotide dithiophosphoramide shows better enzymatic degradation resistance and pharmaceutical stability. In addition, the binding performance between the modified oligonucleotide molecules and environmental ions can be improved through nucleotide dithiophosphamide modification, and a novel chemical modification strategy is provided for research, development and application of oligonucleotide drugs.

The invention discloses synthesis of 5 '-amino-3-nucleotide phosphamide and application of the 5'-amino-3-nucleotide phosphamide in oligonucleotide. The phosphamide modified oligonucleotide comprises a nucleotide structural unit shown as a formula I or a formula II,..., the formula I; ... formula II; through specific limitation of a nucleotide phosphamide monomer structure, the prepared oligonucleotide contains a phosphamide structural unit; compared with a traditional oligonucleotide molecule, the oligonucleotide molecule with the phosphamide modified nucleotide structure has more excellent effects on pharmaceutical parameters such as enzymatic degradation resistance, stability and the like, and in addition, phosphamide modification can improve the binding performance between the modified oligonucleotide molecule and environmental ions; a novel chemical modification strategy is provided for research, development and application of oligonucleotide drugs.

The invention discloses hydrogel loaded with repair-promoting and antioxidant peptides as well as a preparation method and application of the hydrogel, and belongs to the technical field of preparation of medical materials. According to the preparation method, firstly, polypeptide with the amino acid sequence of CEYWVKWCGEKGPAGERG is synthesized, and the polypeptide has antioxidant activity and cell proliferation promoting activity and has good structural stability and enzymatic degradation resistance; and loading the polypeptide into the hyaluronic acid hydrogel to obtain the hyaluronic acid hydrogel. The prepared hydrogel loaded with the repair-promoting and antioxidant peptide has excellent injectable performance and cornea spreadability, can enhance the retention of the polypeptide on the ocular surface, effectively solves the technical problem of high administration frequency of the existing preparation, has good cell and tissue compatibility, and has no adverse reaction in vivo.

The invention relates to the technical field of biological medicine, and particularly discloses application of nucleotide with a 5-oxygen and phosphonic acid embedded spacer group in oligonucleotide. The chemical modification strategy comprises the following steps: preparing a nucleotide phosphoramidite monomer of an O5 '-oxygen and phosphonic acid embedded spacer group; performing solid-phase synthesis on the modified nucleotide phosphoramidite to construct a target oligonucleotide molecule; a spacer group is embedded between oligonucleotide O5 '-oxygen and phosphonic acid, the modified phosphonate structure does not belong to a natural substrate of phosphatase, nuclease degradation can be resisted, and the biological activity of oligonucleotide drugs can be improved.

The invention relates to the technical field of biological medicine, and particularly discloses synthesis and application of oligonucleotide with threose nucleic acid 3-oxygen at the tail end indirectly connected with thiophosphoric acid. The chemical modification strategy comprises the following steps: O < 3->-oxygen of threose nucleic acid is connected with thiophosphoric acid through a spacer group, and O < 2->-hydroxyl is combined with a nucleotide monomer of phosphoramidite; carrying out solid-phase synthesis on the threose nucleic acid O2 '-phosphoramidite monomer to construct an oligonucleotide molecule; the oxygen of the threose nucleic acid at the terminal of the oligonucleotide is linked to the thiophosphoric acid through a spacer group, and since the type of phosphonic acid does not belong to a substrate of phosphatase, the modified oligonucleotide can resist exonuclease degradation and improve its in vivo biological activity.

The application belongs to the technical field of biological medicine, and specifically discloses preparation and application of self-assembled glycopeptide nanoparticles for mRNA vaccine delivery, wherein the nanoparticles are formed by self-assembly of a glycopeptide carrier, mRNA and manganese ions. In the nanoparticle preparation process, the manganese ions are adsorbed onto tryptophan and histidine through metal chelation, and play an adjuvant role in activating the cGAS-STING pathway after administration. The nanoparticles can effectively adsorb mRNA, can stably exist for 4 weeks at 4 DEG C, protect mRNA from enzymatic degradation, promote intracellular mRNA internalization and lysosome escape, effectively transfect eGFP-mRNA and Fluc-mRNA in DC2.4 and BMDC cells, and effectively target mRNA delivery to lymph nodes, activate the cGAS-STING pathway, effectively activate the specific immune system in a B16F10-OVA prevention model, delay tumor growth, and prolong the survival cycle of mice.

The invention discloses a POSTN targeting peptide and a mutant thereof. The POSTN targeting peptide comprises a sequence as shown in SEQ ID NO: 1 and the mutant thereof. The POSTN targeting peptide disclosed by the invention not only has a relatively good blocking effect on POSTN protein, but also has relatively good enzymatic degradation resistance and an effect of inhibiting tumor growth. Moreover, compared with an antibody drug, the POSTN targeting peptide not only has excellent biological activity and biological safety, but also has the advantages of simple structure, easiness in modification and transformation due to carrying of a plurality of functional groups, low synthesis cost and the like.

The invention relates to the technical field of biological medicine, and particularly discloses synthesis and application of oligonucleotide with a spacer group embedded in C4-oxygen and thiophosphoric acid at the tail end. The chemical modification strategy comprises the following steps: connecting C4-oxygen of nucleotide with thiophosphoric acid through a spacer group Y, and combining O3-hydroxyl with a nucleotide monomer of phosphoramidite; carrying out solid-phase synthesis on the nucleotide phosphoramidite to construct an oligonucleotide molecule; c4-oxygen at the tail end of the oligonucleotide is connected with thiophosphoric acid through a spacer group Y, the formed O4-Y-PSO22 < 2-> structure is phosphonic acid in a non-natural form and does not belong to a substrate of phosphatase, and the modified oligonucleotide can resist exonuclease degradation and improve the biological activity of the oligonucleotide.

The invention discloses a real-time monitoring system and method for nano-enzyme degradation polymer dynamics based on plasmon imaging, and the system comprises a monochromatic laser emission module which is used for generating excitation light with a fixed wavelength, and adjusting a light path to excite surface plasmon resonance; the sample reaction module comprises a plasmon resonance gold sheet of which the surface is modified with a polymer molecular layer, and a sample pool for accommodating a reaction solution; the optical detection module is used for collecting and detecting scattered light signals from the sample reaction module and carrying out image acquisition; wherein the monochromatic laser emission module, the sample reaction module and the optical detection module are sequentially connected according to a light path; the invention provides a new important research means for researching the local change of the single nano enzyme and the interaction of biomolecules.

The application of an alkyl radical initiator in the preparation of a scleral collagen cross-linking drug and an oxygen-independent scleral collagen cross-linking method, which utilizes an alkyl radical initiator to cross-link type I collagen solution and scleral tissue, compared with the ultraviolet light / riboflavin cross-linking method, the reaction does not depend on the participation of oxygen, and may be more suitable for the sclera under the hypoxic state of myopia, and compared with the chemical cross-linking method, the cross-linking reaction is easier to control. The alkyl radical-induced collagen cross-linking has improved in terms of anti-enzyme degradation performance, thermal stability and biomechanical performance.

The application belongs to the technical field of food processing, and particularly discloses fish glue polypeptide, a preparation method and application thereof. The preparation method comprises three procedures of acid immersion pretreatment, repeated homogenization and gelatinization treatment and ultrasonic wave assisted immobilized enzyme degradation treatment. The fish glue polypeptide has an average molecular weight of 3.2-8.4 KDa, a molecular weight dispersion coefficient of 0.2-0.5, a small molecular weight, a concentrated molecular weight distribution, a good polypeptide activity, and is beneficial to promoting the absorption of trace elements when applied to fish glue polypeptide-trace element supplement products. When the concentration in the aqueous solution is 2 g / L, the Zeta potential of the micelle is-24 mV to-30 mV, the average particle size of the micelle is 10-20 nm, the particle size dispersion coefficient of the micelle is 0.1-0.2, the average particle size of the micelle is small, the particle size distribution of the micelle is concentrated, the Zeta potential of the micelle is high, and the micelle has good stability.

The invention discloses a double-target-point cyclic peptide and a synthesis method and medical application thereof.The amino acid sequence of the double-target-point cyclic peptide is Cys-Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Alaa-Cys-Lys-Pro-Ser-Trp-Arg-Alaa-Asp, Cys1 and Cys10 form a cyclic peptide structure through disulfide bond cyclization, the relative positions of the N terminal and the C terminal are stabilized, the enzyme resistance and the structural stability are improved, and the double-target-point cyclic peptide has the advantages that the double-target-point cyclic peptide is obtained; further, protease degradation is resisted, the half-life period is prolonged, and efficient analgesia is realized by synergistically activating a mu opioid receptor and inhibiting a voltage-gated sodium ion channel 1.8. The double-target cyclopeptide designed by the invention has the beneficial characteristics of simple structure, convenience in artificial synthesis, low production cost and the like, and has huge medical industrial applicability.

The invention discloses synthesis of 3 '-amido-5-nucleotide phosphamide and application of the 3'-amido-5-nucleotide phosphamide in oligonucleotide. The phosphamide modified oligonucleotide comprises at least one of nucleotide structural units shown in a formula I, a formula II, a formula III or a formula IV,..., the formula I, the formula II, the formula III,..., the formula IV. Through specific limitation of a nucleotide phosphamide monomer structure, oligonucleotides are prepared by coupling according to a direction from 5 to 3. Compared with a traditional oligonucleotide molecule, the oligonucleotide molecule provided by the invention contains phosphamide modification and has more excellent effects on pharmaceutical parameters such as enzymatic degradation resistance, stability and the like, in addition, the phosphamide modification can improve the binding performance between the modified oligonucleotide molecule and environmental ions, and the stability of the oligonucleotide molecule is improved. A novel chemical modification strategy is provided for research, development and application of oligonucleotide drugs.

This invention discloses a logic-responsive biomolecule carrier based on a phase separation system, its construction method, and its applications. The carrier is based on the attraction between cationic peptides with different logic responses and negatively charged biomolecules such as DNA or RNA, driving liquid-liquid phase separation and forming droplet-like particle structures. The carrier of this invention can selectively use protein kinase A (PKA) to phosphorylate peptides and use matrix metalloproteinases (MMPs) or glutathione (GSH) to cleave the peptide chain, thereby changing the charge density of the peptide to control the controlled release of biomolecules. It exhibits excellent biocompatibility, resistance to enzymatic degradation, and transfection efficiency, enabling effective delivery of biomolecules.

The application belongs to but is not limited to the technical field of gene synthesis, and discloses a preparation method of a red blood cell membrane coated framework nucleic acid nanogel, which forms NG through base complementary pairing, and realizes the compounding of RBCm and NG by using an Avanti small extruder.SiRNA is combined and cross-linked with TDN through base complementary to form NG, and the TDN provides the first layer of protection for the siRNA, enhances the stability and drug efficacy of the siRNA, and the red blood cell membrane provides the second layer of protection to prevent enzyme degradation and protein adsorption.M@NG combines the bionics and biocompatibility of RBCm and the high drug loading and stability of NG, and has the characteristics of targeted drug delivery, immune escape and the like.The system is suitable for the treatment of various diseases, and expands the application field of RNA interference technology.

Disclosed are Hematopoietic Progenitor Kinase 1 (HPK1) degradation / disruption compounds including a HPK1 ligand, a degradation / disruption tag and a linker, and methods for use of such compounds in the treatment of HPK1-mediated diseases.

The invention discloses oligonucleotide with a sulfo-modified nucleotide structure and a synthesis process of the oligonucleotide. The oligonucleotide with the sulfo-modified nucleotide structure comprises a nucleotide structural unit as shown in a formula I or a formula II, through specific limitation of a thio-modified nucleotide monomer structure, the synthesized and prepared oligonucleotide contains a thiophosphoramide structural unit; compared with a traditional oligonucleotide molecule, the oligonucleotide sequence molecule with the sulfo-modified nucleotide structure has more excellent effects on pharmaceutical parameters such as drug enzymatic degradation resistance, stability and combinability, and a novel chemical modification strategy is provided for research, development and application of oligonucleotide drugs.

The invention discloses a novel CYP1B1 enzyme degradation agent as well as a preparation method and application thereof, and particularly discloses a CYP1B1 enzyme targeted hydrophobic tag HyT degradation agent which comprises an affinity ligand, a hydrophobic tag and a connecting chain for connecting the affinity ligand and the hydrophobic tag, each of the affinity ligand and the hydrophobic tag comprises an alpha-naphthylflavone derivative; the connecting chain comprises a plurality of repetitive units, and the repetitive units are composed of ethylene glycol fragments or alkyl groups. The invention also discloses a preparation method of the hydrophobic tag HyT degradation agent and application of the hydrophobic tag HyT degradation agent or a pharmaceutical composition thereof. The novel CYP1B1 enzyme degradation agent provided by the invention has stronger CYP1B1 enzyme targeting capability, and can specifically target tumors, realize sensitization anti-PD-L1 monoclonal antibody immunotherapy and enhance the tumor immunotherapy effect.

The invention provides a polypeptide product and omega-3 combined composition and a preparation method thereof. The composition is a nanoparticle with a core-shell structure, and comprises fatty acid modified polypeptide, omega-3 fatty acids and esters thereof, a medium chain triglyceride oil phase, a self-assembly guiding agent and an antioxidant stabilizer. Unsaturated fatty acid and polypeptide with a targeting function are subjected to covalent modification to form an interface anchoring structure, lipid components are effectively entrapped, and the particle size is stabilized; the obtained nanoparticles can respond to release in a specific pH or enzymatic degradation environment, and the local synergistic effect is enhanced. The preparation method comprises the steps of fatty acid modification, oil phase preparation, emulsification shearing, ultrasonic nanocrystallization and the like, the particle size of obtained particles is controlled to be 50-120 nm, and PDI is smaller than 0.3. The invention can be used for targeted therapy of diseases such as neurodegenerative diseases, rheumatoid arthritis, systemic inflammation or metabolic disorders.

The invention relates to the technical field of biological medicines, and discloses a construction method of an inhalation type mRNA vaccine for realizing pulmonary alveolar targeted delivery, which comprises the following steps: selecting lipid nanoparticles or other high polymer materials as a carrier material; carrying out functional modification on the surfaces of the nanoparticles to enhance the lung targeting recognition; chitosan, hyaluronic acid and other high polymer materials are used for wrapping mRNA to form a protective layer, and oxidation and enzymatic degradation are reduced; the flow characteristics of airflow in a lung airway are calculated based on a fluid dynamics model, and distribution of particles in the lung is optimized by combining with a nano particle diffusion model. Accurate control and stable expression in the mRNA delivery process are achieved, the in-vivo delivery efficiency and mRNA stability are remarkably improved, the effective expression time is prolonged, the tissue damage risk is reduced, the intelligent level and physiological environment adaptability of a delivery system are integrally enhanced, and the method is suitable for vaccine delivery and gene therapy application scenes with high requirements.

The application relates to the technical field of PET plastic degradation, and discloses a process for degrading PET plastic by using enzymes, which comprises the following steps: etching the surface of PET plastic by using plasma to introduce carboxyl groups and hydroxyl groups on the surface of the PET plastic; covalently combining boric acid-based compounds with the hydroxyl groups on the surface of the PET plastic through boric acid ester bonds to form a grafted layer on the PET surface; and degrading the PET plastic after the grafting treatment by using modified polyester hydrolytic enzymes. The application accurately constructs regular and spaced binding sites on the PET surface by using a mask-guided nanosphere template etching technology, the spacing design is based on the effective catalytic radius of a PETase enzyme molecule, each enzyme molecule has an independent and sufficient catalytic working area, and space steric hindrance and substrate competition between adjacent enzyme molecules are avoided.

Disclosed are hematopoietic progenitor kinase 1 (HPK1) degradation / destruction compounds comprising an HPK1 ligand, a degradation / destruction tag, and a linker group, and methods of using such compounds in the treatment of HPK1-mediated diseases.

Provided are compounds of Formula (I), a tautomer thereof, a deuterated derivative of the compound or the tautomer, and a pharmaceutically acceptable salt of the foregoing, compositions comprising the compounds of Formula (I), a tautomer thereof, a deuterated derivative of the compound or the tautomer, and / or a pharmaceutically acceptable salt of the foregoing, and methods of using the same, in treating, for example, the diseases, disorders, or conditions mediated by the degradation of protein kinases, such as Hematopoietic progenitor kinase 1 (HPK1, MAP4K1), Mitogen-activated protein kinases 1 / 2 (MEK 1 / 2), Human Fms-like tyrosine kinase 3 receptor (FLT3), and Aurora kinases.

The present invention discloses a controllable electric field-enhanced enzymatic degradation method and application for in-situ remediation of organic contaminated soil, belonging to the technical field of in-situ remediation of organic contaminated soil. The method comprises the following steps: setting electrode wells in the remediation area, the electrode wells being arranged in a rectangular shape to form a non-uniform symmetrical electric field; inserting electrodes into the electrode wells, fixing them, and connecting them to the corresponding output ends of a DC power supply; pumping an electrolyte containing immobilized enzymes into the anode wells and into the cathode wells; setting the potential gradient of the electric field for transporting the immobilized enzymes and starting the DC power supply; after completing the electrokinetic transport of the immobilized enzymes, adjusting the DC electric field potential gradient and starting electrokinetic enhanced degradation. The present invention achieves low-carbon, green in-situ remediation of organic contaminated soil based on enzyme bioelectrochemical degradation and microelectrode redox pathways.

The invention discloses synthesis of 5 '-amino-3-nucleotide thiophosphoramide and application of the 5'-amino-3-nucleotide thiophosphoramide in oligonucleotide. The thiophosphoramide modified oligonucleotide comprises a nucleotide structural unit shown as a formula I or a formula II,..., the formula I; ... formula II; through specific limitation of a nucleotide thiophosphoramide monomer structure, the prepared oligonucleotide contains a thiophosphoramide structural unit. Compared with a traditional oligonucleotide molecule, the oligonucleotide molecule with the thiophosphoramide modified nucleotide structure has more excellent effects on pharmaceutical parameters such as enzymatic degradation resistance, stability and the like, and in addition, the binding performance between the modified oligonucleotide molecule and environmental ions can be improved through thiophosphoramide modification; a novel chemical modification strategy is provided for research, development and application of oligonucleotide drugs.

A method of nucleic acid amplification involving using a first modified primer which provides protection to the amplification product from exonuclease degradation and a second primer. The method provides a double stranded nucleic acid, one strand of which is degraded by a double strand nucleic acid specific exonuclease to form a single stranded nucleic acid, which is protected from exonuclease degradation.

The invention belongs to the technical field of medicines, and discloses a nano preparation for tumor immunotherapy as well as a preparation method and application of the nano preparation. According to the preparation method disclosed by the invention, the siRNAPD-L1 is successfully entrapped in the ZIF-8 by virtue of an electrostatic adsorption effect and a self-assembly method, and finally, the ZIF-8 nano preparation entrapped with the siRNAPD-L1 is prepared. The method is simple in preparation process, low in cost, good in stability and high in repeatability. The metal organic framework nanoparticles provided by the invention are helpful for solving the problems that siRNAPD-L1 is unstable in systemic circulation and is easily degraded by enzyme, and the like, and also overcomes the difficult problems that siRNAPD-L1 has obstacles in the aspects of in-vivo system circulation, tissue permeation, cell absorption, endosome escape and the like due to large molecular weight, strong water solubility and negative charge characteristics; therefore, the delivery efficiency and the anti-tumor effect of the siRNAPD-L1 are improved. The nano-composite is simple and rapid in preparation process, is easy for large-scale and industrial production, and also has a better development prospect in the aspect of clinical application transformation.