60 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 efficient continuous PET (polyethylene terephthalate) degradation process based on a membrane method technology, which comprises the following steps: mixing an immobilized enzyme compound, a PET raw material to be degraded and a glycine buffer solution to form a reaction solution for degradation, then constructing a'continuous reactor 'by using two size screening membranes, performing primary separation by using an ultrafiltration membrane or a microfiltration membrane, and performing secondary separation by using an ultrafiltration membrane or a microfiltration membrane. A nanofiltration membrane or a reverse osmosis membrane is adopted for secondary separation of the degradation product, automatic separation of the degradation product and a reaction system and automatic purification of the degradation product are achieved, and then the enzymatic degradation efficiency and the product recovery efficiency are improved. Through the construction of the continuous reactor, the automatic PET degradation is realized, so that the costs in the aspects of labor, time, economy and the like are remarkably saved. The undegraded PET and a small amount of exfoliative enzyme can be circulated back to the reaction kettle after being intercepted by the size screening membrane, and the process not only can promote full contact between the undegraded PET and the hydrolase, but also can reduce the loss of the enzyme in the degradation process.

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 a nanocapsule for targeting glioma containing a Cas9 / sgGDF15 compound as well as a preparation method and application of the nanocapsule, and belongs to the technical field of biological medicines. According to the nanocapsule disclosed by the invention, the glioma targeting peptide Ang with strong brain penetrating power is cross-linked on the surface, so that the glioma targeting property of the nanocapsule is improved; a disulfide bond is added on the surface of the nanocapsule, so that the nanocapsule can be prevented from being degraded by enzyme action in blood, and a Cas9 / sgGDF15 compound entrapped in the nanocapsule can be ruptured and accurately released in a high glutathione microenvironment at a tumor part of the nanocapsule, so that the GDF15 gene of glioma cells is efficiently edited, and the GDF15 gene in the glioma cells is specifically knocked out; the immunosuppressive microenvironment of the glioma is reversed, the anti-tumor effect of immune cells is recovered, and the aim of treating the glioma is achieved.

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.

Described herein, in part, are compounds that mediate the degradation of casein kinase 1α (CK1α), and are therefore useful in the treatment of various disorders, such as cancer.

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 belongs to the technical field of biological medicine, and particularly discloses preparation and application of self-assembly glycopeptide nanoparticles for mRNA vaccine delivery, and the nanoparticles are formed by self-assembly of glycopeptide carriers, mRNA and manganese ions. In the preparation process of the nanoparticles, manganese ions are adsorbed to tryptophan and histidine through metal chelation, and the adjuvant effect of activating a cGAS-STING pathway is achieved after administration. The nanoparticle can effectively adsorb mRNA, can stably exist at 4 DEG C for 4 weeks, can protect mRNA from enzymatic degradation, can promote mRNA internalization and lysosome escape, can effectively transfect eGFP-mRNA and Flucc-mRNA in DC2.4 and BMDC cells, can effectively deliver mRNA to lymph nodes in a targeted manner, activates a cGAS-STING pathway, effectively activates a specific immune system in a B16F10-OVA prevention model, delays tumor growth, and can be used for preparing a drug for preventing cancer. The mouse life cycle is prolonged.

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 discloses an analysis method for catalytically degrading microplastics based on laccase. The analysis method comprises the following steps: pretreating microplastic particles; determining an optimal experiment condition for degrading the microplastics by the laccase; uniformly mixing the pretreated micro-plastic with the determined laccase solution under the optimal experiment condition according to a certain proportion, carrying out a degradation experiment in a constant-temperature oscillator, and regularly sampling and analyzing; the reaction suspension obtained after regular sampling is filtered through a filter membrane, supernate and solid are obtained, the supernate is used for degradation product analysis, and the solid is used for physicochemical characteristic characterization analysis; and analyzing the sample by using an ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry technology. According to the qualitative and quantitative analysis method based on laccase catalytic degradation of the microplastics, the experiment conditions of laccase degradation of the microplastics are optimized, an efficient detection technology is combined, and compound variants generated in the degradation process can be accurately and quantitatively analyzed.

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 invention provides nano microspheres for targeted delivery of siRNA based on SFTSV-Gn and application of the nano microspheres, and belongs to the technical field of antiviral drugs. SiRNA is optimally designed, a nano microsphere delivery system is a nano compound formed by assembling optimally designed siRNA and cell-penetrating nano arginine, and the nano microspheres are used as a delivery carrier of siRNA to protect siRNA from enzymatic degradation, so that the siRNA delivery efficiency is improved, and the siRNA delivery efficiency is improved. And the target cells can be promoted to uptake, the replication of new bunyavirus RNA (Ribonucleic Acid) can be effectively inhibited, the injury of liver and lung tissues can be improved, and the survival rate can be increased. In addition, the surface-modified nano-microspheres have the advantages of high targeting, deep penetration, non-invasiveness and the like, and have wide application prospects in the antiviral field.

The invention provides plastic waste recovery and fragmentation equipment, and relates to the technical field of waste recovery devices.The plastic waste recovery and fragmentation equipment comprises a box body, a pair of fragmentation rollers and a grinding roller are arranged above the box body, an enzymatic degradation inner cavity is formed in the position, below the grinding roller, of the box body, and a magnetized particle bearing cylinder is installed in the enzymatic degradation inner cavity in a fixed-axis rotating mode; magnetic adsorption grooves are formed in the outer edge of the magnetized particle bearing cylinder in an annular array mode, magnetic enzymatic degradation particles are placed in the magnetic adsorption grooves, the liquid spraying plates are fixedly installed in the tangential direction above the grinding roller, and the surface of the grinding roller is cleaned through liquid pumped out by the liquid spraying plates. According to the invention, the magnetic enzyme degradation particles are used for biodegradation of crushed plastic, compared with the existing physical crushing mode, the biodegraded substances have higher environmental friendliness, the magnetic adsorption characteristic of the magnetic enzyme degradation particles is fully utilized, the magnetic enzyme degradation particles are convenient to recycle and reuse, and the method is more energy-saving and environment-friendly.

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.

Described herein, in part, are compounds that mediate the degradation of casein kinase 1α (CK1α), and are therefore useful in the treatment of various disorders, such as cancer.

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.

The invention belongs to the technical field of anti-bladder cancer drugs, and discloses an IL 12mRNA lipid nanoparticle, which comprises IL 12mRNA and a carrier for delivering the IL 12mRNA, and the carrier comprises one or more amino acid tocopheryl oxyalkyl esters or pharmaceutically acceptable salts of the amino acid tocopheryl oxyalkyl esters. The invention further discloses a preparation method of the lipid nanoparticles and application of the lipid nanoparticles in preparation of bladder cancer resisting drugs. According to the lipid nanoparticle, amino acid tocopheryl oxyalkyl ester serves as an ionizable lipid molecular carrier for delivering IL12mRNA, the IL12mRNA is effectively delivered into tumor cells, the risk that mRNA is degraded by enzyme is avoided, meanwhile, the lipid nanoparticle plays an anti-tumor role in a mouse bladder cancer treatment group, the growth of cancer cells is inhibited, and the lipid nanoparticle has good biological safety.

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 present invention belongs to the field of microbial technology, and particularly relates to a bacillus mutant strain of a high-yield alkaline mannanase and its application technology. The strain is specifically Bacillus licheniformis (Bacillus licheniformis) GAN2-10, with a deposit number of CGMCC NO.26080. The mannanase enzyme activity produced by the fermentation of the mutant strain reaches 35980U / mL, which is more than 40% higher than the mannanase enzyme activity produced by the original strain. The optimum reaction temperature of the obtained mannanase is 40°C, and a good enzyme degradation effect can be exerted in a low temperature environment, and it has good heat resistance, and after being incubated for 4h at 80°C, the relative enzyme activity is more than 80%. In addition, the enzyme has an optimum reaction pH of 9.5, has good alkali resistance, and after being incubated for 4h at pH 11.0, the relative enzyme activity is more than 85%. Due to the good enzymatic properties of the above-mentioned enzyme, it can exert a good enzymolysis effect in a low temperature and alkaline environment, so it can be widely used in industries such as decolorization and bleaching.

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.

The present invention relates to a chitosan derivative modified with 2-imidazolinone, and a preparation method and application thereof. The present invention adopts a strongly electrophilic isothiocyanate reagent to react with the 2-amino group of chitosan to construct an imidazolinone ring under heating conditions, and has the advantages of high yield and simple operation. The prepared chitosan derivative modified with 2-imidazolinone ring has good water solubility and has good anti-Escherichia coli activity after enzyme degradation.