153 results about "Covalent binding" patented technology

The present invention relates to a compound binding to an endogenous receptor, said compound comprising (i) an oligopeptide comprising a dipeptide with Trp being the C-terminal amino acid of said dipeptide, wherein said Trp is replaced with an α-amino acid Xaa2, whereby the stability in serum or plasma of the peptide bond connecting Xaa2 to the N-terminally adjacent amino acid is increased as compared to the peptide bond connecting Trp to the N-terminally adjacent amino acid in an otherwise identical compound; and (ii) a moiety capable of generating therapeutically effective radiation, said moiety being covalently bound to said oligopeptide.

The invention discloses an electrochemical biosensor for detecting mycobacterium tuberculosis. The sensor takes a porous membrane as a base material, the inner wall of a pore channel of the porous membrane is co-modified with a polydopamine (PDA) and conductive carbon material composite layer, and an amino-modified specific capture probe based on a mycobacterium tuberculosis ESAT-6 gene is fixed on a modification layer through covalent binding. When a target gene is captured by a probe, the volume effect of the target gene causes blockage of a porous channel of the porous membrane, so that electrochemical signals (such as current) of the sensor are changed, and high-sensitivity and specific detection of mycobacterium tuberculosis is realized. According to the invention, a porous structure, biological probe specific fixation and an electrochemical signal conversion technology are combined, and a novel efficient tool is provided for rapid diagnosis of tuberculosis.

The invention belongs to the technical field of biological medicine, and particularly relates to hyaluronic acid nano-microspheres as well as a preparation method and application thereof. According to the preparation method of the hyaluronic acid nano-microspheres, the hyaluronic acid nano-microspheres are prepared through interaction of nucleic acid, basic amino acid and hyaluronate in a specific proportion, the preparation process is optimized, and the prepared hyaluronic acid nano-microspheres are high in hyaluronic acid adding amount, high in skin permeability and good in skin care effect. The stability is good, and the application requirements in transdermal drug delivery drugs, skin care products and other products are met. Meanwhile, a non-covalent binding mode is adopted for preparing the nano-microspheres, the preparation operation is simple, the gelling property of the hyaluronate is effectively improved, the sticky feeling under high content is improved, and the application scene of hyaluronic acid in the field of skin care products is widened.

The invention discloses a PROTAC chimera for targeted degradation of an ROR [gamma] t receptor and application of the PROTAC chimera, the structure of the chimera is RW-L-Re, Re is a ligand capable of being combined with E3 ubiquitin ligase, L is a linking group covalently combined with at least one Re and at least one RW, and Rw is a target protein ROR [gamma] t binding ligand and is selected from one of the following structures. A series of PROTAC chimeras capable of degrading an ROR gamma t receptor in a targeted manner are designed and synthesized for the first time, a ternary complex is formed mainly by combining a target protein ligand and an E3 ubiquitin ligase ligand with POI and E3 ligase respectively, and then the POI is labeled with a ubiquitination tag and is further degraded by proteasome. Experimental results prove that the PROTAC chimera designed by the invention has excellent ROR [gamma] t receptor degradation activity, and can be used for preparing related drugs for treating autoimmune diseases or tumors.

The invention belongs to the field of environmental biotechnology and nano material application, and relates to a method for accelerating microorganisms to reduce selenite based on immobilized riboflavin. Aiming at the problems of poor stability, difficulty in recovery, non-repeated use and the like of dissolved riboflavin serving as an electron shuttle, riboflavin is grafted on the surface of a multi-walled carbon nanotube through a covalent binding method, and immobilized riboflavin capable of being recycled is constructed. The material can accelerate extracellular electron transfer of shewanella MR-1, and toxic sodium selenite is efficiently reduced into low-toxicity or non-toxic elemental selenium. Results show that the immobilized riboflavin not only maintains high reduction activity of riboflavin, but also has excellent cyclic utilization performance, still maintains high reduction rate after being repeated for multiple times, and effectively reduces operation cost and resource loss. According to the invention, an efficient, economical and sustainable application scene is provided for a microorganism-electron shuttle combined remediation technology, and a new thought is also provided for application of a functional nano material in an environmental biotechnology.

The invention belongs to the technical field of lipase immobilization, and particularly relates to immobilized lipase and a preparation method thereof. The preparation method comprises the following two steps: (I) preparation of activated amino type silica gel resin: mixing amino type silica gel resin, a nonionic surfactant 1308 and deionized water according to a mass ratio of (1000-1100): (2000-2200): (5-8), stirring at 1-5 DEG C for 10-15 minutes, adding cyanuric chloride, dripping a 30-35 wt% sodium hydroxide solution, reacting, and centrifuging; (II) preparation of immobilized lipase: mixing the activated resin, a surfactant, deionized water and a lipase solution, dropwise adding an alkaline solution at 40-45 DEG C under the condition that the pH is 5.0-5.5, and centrifuging, washing and drying after reaction. The obtained immobilized lipase is firm in covalent binding, the enzyme activity is greater than or equal to 50% after the immobilized lipase is repeatedly used for 6 times, the acid-base tolerance and the storage stability are excellent, and the immobilized lipase is suitable for industrial catalysis in multiple industries.

A method is provided for treating a subject with cancer using a recombinant polypeptide comprising a DRα1 domain containing a glutamine residue at the position corresponding to amino acid 45 of SEQ ID NO: 1 or SEQ ID NO: 2, or an antigenic peptide covalently bound to a portion thereof. In some cases, the subject has a tumor that is resistant to immune checkpoint blockade treatment and / or does not express a BRAF mutation. The present invention provides, for example, a method for treating a subject with cancer, comprising administering to the subject a therapeutically effective amount of a recombinant polypeptide comprising a DRα1 domain containing a glutamine residue at the position corresponding to amino acid 50 of SEQ ID NO: 1 or SEQ ID NO: 2, or an antigenic peptide covalently bound to a portion thereof; or a nucleic acid encoding the recombinant polypeptide.

The application discloses a kind of detection flavonoid compound magnetic composite material, preparation, detection method and the application of preparation standard substance, belong to analytical chemistry technical field.Magnetic composite material includes magnetic nanoparticle core, double lanthanide series metal organic framework (MOF) first shell and covalent organic framework (COF) second shell successively coated on its surface, and phenylboronic acid group grafted on the surface of second shell.The material uses the specific covalent binding of phenylboronic acid and the characteristic ortho-diphenol hydroxyl group of flavonoid compound to realize efficient capture and enrichment;Through double lanthanide series MOF shell, promote energy transfer, COF shell provides high specific surface area and ordered diffusion channel, and magnetic core is convenient for rapid separation, which realizes high selectivity identification of flavonoid compound.The material has the advantages of high sensitivity, strong anti-matrix interference ability, rapid and simple detection, etc., and is suitable for accurate analysis of flavonoid compound in complex sample and development of related standard substance.

Methods of analyzing a fecal sample containing parasitic material and non-parasitic material are disclosed. The method may include combining the fecal sample with a flotation medium in a container. The method may further include at least partially separating the parasitic material and non-parasitic material in the flotation medium. The method may further include extracting at least a portion of the parasitic material from the flotation medium. The method may further include staining or labeling the extracted parasitic material with a fluorochrome comprising a functional group reactive with a functional group of the parasitic material, where the fluorochrome may bind to the parasitic material via a covalent bond. The method may further include placing the labeled parasitic material within an imaging unit for imaging and analysis of the labeled parasitic material.

A method for producing hydrophobic dry surface-modified fibrillated cellulose to improve dispersion in hydrophobic matrices includes: providing micro-fibrillated cellulose suspension of 5-30 wt % in water; adding a surfactant to the suspension with a mass ratio of surfactant to micro-fibrillated cellulose suspension of 0.1-2.0 wt %; adding a surface modifier to the suspension with a mass ratio of surface modifier to micro-fibrillated cellulose dry matter of 20-300 wt %, with the surface modifier obtained through a chemical reaction of a silane compound with a phenolic compound to create covalent bonds between the silane compound and the phenolic compound; covalently binding the surface modifier to the micro-fibrillated cellulose via (i) hydrolysis of the surface modifier to form reactive silanol groups and (ii) condensation of the silanol groups with available OH-groups of the micro-fibrillated cellulose; adding a plasticizer to the suspension of surface modified micro-fibrillated cellulose; drying the suspension.

The invention belongs to the technical field of hydrogel preparation, and relates to a preparation method and application of metabolism programming hydrogel, and the preparation method comprises the following steps: 1, oxidizing dextran Dex through sodium periodate NaIO4 to generate oxidized dextran ODex rich in aldehyde; 2, under the protection of nitrogen, carrying out amino dynamic Schiff base reaction of APTC and carrying out covalent binding with an aldehyde group of oxidized dextran ODex to form ODex-APTC; 3, mixing ODex-APTCC and CMC GOx solutions at room temperature to form hydrogel based on hemiacetal crosslinking and a hydrogen bond mechanism; according to the invention, autonomous'antibacterial repair 'dual-phase switching is realized through metabolic microenvironment reprogramming; in the stage of wound surface high-glucose infection, the hydrogel utilizes a diabetes wound surface high-glucose environment as an endogenous fuel, and glucose reduction, active oxygen mediated sterilization and microenvironment acidification are realized at the same time through reaction of glucose oxidase and glucose; when glucose oxidase reacts, the acid environment triggers a controlled H2S release program, and wound healing is accelerated by relieving oxidative stress and activating a regeneration signal channel.

The invention discloses a functionalized microarray pore plate, a preparation method thereof and application of the functionalized microarray pore plate in membrane protein ligand screening, and belongs to the technical field of biological medicine analysis. Amino and vinyl sulfuryl are covalently modified on the surface of the microarray pore plate to introduce an active site which can be specifically covalently bound with a membrane protein or a tag group, so that directional fixation of a target membrane protein on the surface of the microarray pore plate is realized, and the functionalized microarray pore plate is obtained. A functional microarray pore plate and a specific fluorescent probe are combined to screen a membrane protein ligand, the specific fluorescent probe is combined with a receptor active site of a fixed protein, and a detectable fluorescence signal change is generated by utilizing a competitive replacement mechanism of the probe and a candidate compound at the active site; the method is used for in-vitro screening and discovery of potential membrane protein ligands.

The invention discloses a method for detecting active watermelon bacterial fruit blotch bacteria by a PMA-PCR (Polymerase Chain Reaction) technology, which comprises the following steps: (1) collection and suspension of bacteria in a sample to be detected: suspending the sample with normal saline to obtain a bacterial suspension; (2) PMA treatment: adding propyl azide bromide (PMA) into the bacterial suspension; (3) blue light crosslinking: irradiating the bacterial suspension treated by the PMA under blue light to activate the covalent binding of the PMA and dead bacteria DNA (Deoxyribose Nucleic Acid); (4) DNA extraction: centrifugally collecting thalli, and extracting DNA by adopting a kit method; (5) PCR amplification: carrying out amplification by using a specific primer pair; and (6) result judgment: detecting an amplification product through agarose gel electrophoresis, wherein a target strip appears in an active bacterium sample, and no strip exists in a dead bacterium sample. The invention establishes a rapid, convenient, accurate and efficient method for detecting the active watermelon bacterial fruit blotch, so as to improve the disease detection capability and management efficiency.

A process for synthesizing and separating secretory IgA from a mixture of IgA monomer and IgA dimer is provided The process includes covalently binding affinity tagged or epitope tagged recombinant secretory component to the IgA dimer in the mixture and then binding the affinity tagged or an epitope tagged secretory IgA to immobilized moieties on the solid phase support resin to which the affinity tag or epitope tag binds and then eluting the affinity tagged or an epitope tagged secretory IgA with release buffer. A process for synthesizing and separating secretory IgM from a mixture of IgM and other plasma proteins is provided. A process is provided for inhibiting or preventing symptoms of necrotizing enterocolitis in a subject that includes the oral administration to the subject of a human polyclonal secretory IgA formed by the conjugation of human recombinant secretory component and pooled human plasma derived dimeric and polymeric.

A nanoparticle complex comprises a bifunctional conjugate capable of non-covalently binding to lipid nanoparticles in the nanoparticle complex.

Provided herein is a particle made of a protein covalently bound to a prebiotic carbohydrate, thereby forming a conjugate, wherein at least two said conjugates are covalently crosslinked via their carbohydrate units (e.g. by a phospho-di-ester bond). The said particle may be used for selectively promoting probiotic bacteria growth in the colon and may be used to deliver additional probiotic growth factors, or other bioactives and drugs to the colon. Furthermore, provided herein are methods for preparing the particle, and for delivering a substance bound to, or entrapped within the particle, into the gastrointestinal tract of a subject in need thereof.

The present invention discloses a collagen matrix flap covalently bound to fibroblast growth factor and a preparation method thereof. The collagen matrix flap is prepared by cross-linking oxidized sodium alginate (OSA) and bovine type I collagen. Subsequently, polyamide-amine dendrimer (PAMAM) is used as a connection carrier to covalently graft basic fibroblast growth factor (bFGF), thereby constructing a scaffold system capable of long-term sustained release of growth factors. The scaffold has good biocompatibility. Experiments have shown that the scaffold of the present invention exhibits clinical operability, superior biological activity to other growth factor-loaded scaffolds, and a more sustained growth factor release effect.

This invention discloses a type of click-type covalent drug, its regionally selective delivery system, and its applications. The invention comprises two parts: a click-type covalent drug and a tumor regionally selective delivery system. The click-type covalent drug consists of three parts: an azacyclic alkyne (DBCO), a small molecule drug, and a linker, having the structure of Formula 1. Optionally, the small molecule drug is a membrane protein inhibitor, an immunomodulator, or a chemotherapeutic drug. The click-type covalent drug reacts with azide-labeled target cells via a click reaction, forming a covalent bond that binds to the cell membrane, increasing the local drug concentration and prolonging the drug retention time, thereby enhancing selective inhibition of the target cells. The regionally selective delivery system is co-assembled from an amphiphilic block polymer and the click-type covalent drug for regionally selective delivery. This invention achieves covalent binding to azide-labeled tumor cells through the click-type covalent drug, while having no effect on unlabeled normal cells, reducing toxic side effects on normal tissues.

The invention provides a double-layer high-swelling hydrogel microneedle as well as a preparation method and application thereof, and belongs to the technical field of hydrogel microneedle materials. According to the invention, the N, N '-methylene bisacrylamide and polyethylene glycol dimethacrylate double cross-linking agents are utilized to improve the cross-linking efficiency and network uniformity of the gel and enhance the rigidity and toughness of the microneedle; the medicine Col is only loaded on the first layer of the needle tip, so that the microneedle does not cause inflammatory stimulation to the skin, and the utilization rate of the medicine on the needle tip is improved; a GO.Apt compound in the second-layer structure of the needle tip is used as a sensor, so that the microneedle can be used for uric acid marker sampling and specific detection; the carboxylated graphene oxide GO can be used as a quenching group of a sensor GO.Apt compound, and the mechanical property of the microneedle is enhanced; the covalent binding of the Apt. And the GO avoids the release of the Apt. And ensures the performance of the sensor; the microneedle provided by the invention has good morphology, can be effectively inserted into skin, and realizes release of drugs and extraction of skin interstitial fluid.

The present invention relates to polypeptides which are covalently bound to aromatic molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of PD-L1. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and / or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by PD-L1.

This invention discloses a method for detecting adiponectin in human serum using a polydopamine-modified wire mesh carbon electrode, specifically relating to the field of adiponectin detection technology. The method involves preparing a 2 mg / mL dopamine hydrochloride solution using a 10 mM tris(hydroxymethyl)aminomethane hydrochloride buffer solution (pH=8.5) and adding it dropwise onto the surface of the working electrode. A polydopamine-modified layer is formed by electropolymerization within a range of -800 mV to 600 mV using cyclic voltammetry. A conductive layer of a poly(3,4-ethylenedioxythiophene)-polystyrene sulfonic acid complex is then coated. Adiponectin antibodies are then immobilized on the surface of the modified layer via covalent binding of amino and quinone groups. After specific binding with a serum sample, the oxidation peak current change is read out from -100 mV to 350 mV in a buffer detection medium containing 5 mM ferricyanide redox pairs, and the concentration is output from a standard curve. This method improves the density of antibody immobilization sites and inhibits non-specific serum adsorption, enhancing signal stability and sensitivity, and enabling rapid, low-cost quantitative detection of trace amounts of serum.

The invention relates to the technical field of special glass, and discloses special protective glass and a preparation method thereof.The special protective glass comprises a glass substrate and a self-healing coating coated on the surface of the glass substrate; the glass substrate consists of oxides of the following elements: a silicon source, an aluminum source, a lithium source, a sodium source, a magnesium source, a zirconium source, a phosphorus source, a titanium source, a cerium source and a tin source; the self-healing coating comprises an organosiloxane film forming component, a crosslinking component, a silane anchoring component and nanoparticles; the cross-linking component comprises a boric acid ester bond cross-linking structure and a disulfide bond cross-linking structure; the silane anchoring component comprises at least one molecule with a trialkoxy silicon group at the tail end, and the self-healing coating is combined with a silanol group on the surface of the glass substrate through a silicon-oxygen bond to form an interface covalent binding layer. According to the invention, the glass can be effectively repaired after cracks appear, so that not only is the optical performance ensured, but also the mechanical strength of the glass is enhanced.

The invention relates to an MDM2 protein targeted fluorescent probe, an MDM2 protein targeted degradation fluorescent probe and a preparation method and application thereof.The MDM2 protein targeted fluorescent probe comprises fluorescent molecules and multifunctional polypeptide which are connected with each other, and the multifunctional polypeptide comprises alkynyl, a fluorine-substituted aryl fluorosulfate structure and MDM2 protein targeted peptide; and reacting the fluorescent molecule with alkynyl of the multifunctional polypeptide to obtain the MDM2 protein targeting fluorescent probe. According to the present invention, the fluorine-substituted aryl fluorine sulfate structure on the multifunctional polypeptide can be subjected to specific covalent binding with the MDM2 protein, and the fluorescent molecule and the MDM2 protein interact so as to allow the fluorescent probe to release the fluorescent signal, such that the detection of the intracellular MDM2 protein is achieved. Compared with the MDM2 protein targeted fluorescent probe, the MDM2 protein targeted degradation fluorescent probe has the advantages that the E3 ubiquitin ligase recruitment peptide is added, so that the degradation of MDM2 protein in cells can be induced, and the degradation process can be monitored in real time.

Methods for nucleic acid sequencing include providing at least one device comprising a first electrode and a second electrode separated by a dielectric layer, and a polymerase attached to a surface of the dielectric layer. The dielectric layer induces an electroactive molecule to interact with the electrodes to complete an electrical circuit. The polymerase targets a polynucleotide strand to the dielectric layer. A sample comprising the polynucleotide strand and a modified nucleotide having an electroactive label covalently bound to a 3'-OH of a sugar ring of the nucleotide via an ester group is provided to the at least one device. An electrical potential is applied to each electrode to induce a flow of electrons between the electrodes to produce a measurable electrical signal when the electroactive label is present in the dielectric layer. The electrical signal from the electrodes is detected to determine when the modified nucleotide is present in the dielectric layer.

The present invention relates to polypeptides which are covalently bound to non-aromatic molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of the Eph receptor tyrosine kinase A2 (EphA2). The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and / or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder characterised by overexpression of EphA2 in diseased tissue (such as a tumour).

Provided herein is a platform technology for designing stabilized peptides that covalently bind their target protein and thereby inhibit the activity of the target protein. Also provided are exemplary stabilized peptides that can be used for covalent modification of their target proteins.

The instant invention concerns a process for fragmenting a polymer chain, comprising an oxidative degradation step wherein the polymer chain is contacted with a reduced form of a metal M and an oxidant such as dioxygen, and wherein the polymer carries covalently bound chemical groups acting as a ligand of said reduced form of the metal M.The invention also relates to methods making use of this fragmentation process as a first step of a degradation process of the polymer especially useful for avoiding the negative impact of a polymer to the environment. In this connection, the invention relates to the use of polymers carrying chemical groups acting as a ligand for a reduced form of a metal M, as a polymer biodegradable in an environment wherein the reduced form of a metal M is present.

This invention provides novel and improved delivery technologies that enable systemic and / or local delivery of various gene-based therapeutics, including antisense oligonucleotides (ASOs). [Solution] The present invention provides novel compounds useful for the delivery of various nucleic acids and genes, compositions and formulations of liposomes, microbubbles and / or nanodroplets, and emulsions thereof, as well as methods for preparing them and methods for using them, including imaging and gene delivery methods using sonic activation. In one embodiment, a complex is provided comprising a compound non-covalently bound to a nucleic acid molecule to form a complex, wherein the compound comprises a nucleoside covalently bonded to one or more alkyl groups having at least nine carbon atoms, and the nucleic acid molecule comprises an ASO.

The disclosure describes a fusogenic liposome-coated porous silicon nanoparticles for high loading efficiency of anionic payloads (small molecules, dyes, nucleic acids), and for non-endocytic delivery of hydrophilic and lipophilic payloads by membrane fusion. The liposome coating can be further modified with targeting peptides or antibodies via covalent binding chemistry between the ligands and functionalized poly(ethylene glycol). The surface moieties can be transferred to the cellular membrane surface by fusogenic uptake. The composition of the disclosure can be applied in the treatment of diseases by delivering entrapped / encapsulated payloads.

This invention belongs to the field of pharmaceutical technology and relates to a composite nanoparticle that synergistically induces ferroptosis and antitumor immune responses, as well as its preparation method. The invention first provides a dihydroartemisinin dimer prodrug or a pharmaceutically acceptable salt thereof with the following structure. Then, composite nanoparticles are prepared using the aforementioned dihydroartemisinin dimer prodrug or its pharmaceutically acceptable salt as the main drug component. The composite nanoparticles are prepared by covalently binding an albumin-manganese dioxide complex and ferritin, while simultaneously co-encapsulating the dihydroartemisinin dimer prodrug or its pharmaceutically acceptable salt and a photosensitizer. The composite nanoparticles prepared by this invention can disrupt the reducing homeostasis of tumor cells by simultaneously enhancing ROS generation and GSH consumption. PDT and CDT synergistically enhance ROS generation, and manganese dioxide can also promote GSH consumption. These composite nanoparticles can significantly improve drug targeting and significantly enhance antitumor activity.