94 results about "Covalent binding" patented technology

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 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.

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.

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.

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 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.

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.

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.

The application discloses a mussel-mimic bacterial-responsive injectable hydrogel and a preparation method and application thereof, and belongs to the technical field of biological medicines. The hydrogel is composed of a mussel-mimic viscous hydrogel support and a bacterial response agent; the viscous hydrogel support is QCS-EC, which is formed by non-covalent combination of quaternary ammonium chitosan QCS and epigallocatechin gallate EGCG; and the bacterial response agent is a supramolecular nanometer cross-linking compound TEBox-B 12， which is self-assembled by hydrogen bonds and electrostatic interactions. 12 H 12 2‑ The hydrogel of the application has NIR-II photothermal and photodynamic antibacterial treatment functions, can realize efficient killing of bacteria in deep tissues, has high adhesion, good biocompatibility and injectability, is convenient and applicable, can provide a good healing environment for a wound, promotes fibroblast proliferation and migration, accelerates wound tissue regeneration and healing process, and reduces scar formation.

The invention provides a surface hydroformylation bamboo powder composite material, the surface hydroformylation bamboo powder composite material comprises surface hydroformylation bamboo powder particles and amino biomacromolecules, the surfaces of the surface hydroformylation bamboo powder particles are provided with hydroformylation cellulose nanofibers, hydroformylation cellulose nanosheets and hydroformylation lignin, wherein one ends of the aldehyde cellulose nanofibers and the aldehyde cellulose nanosheets are embedded into the bamboo powder particles, and the other ends of the aldehyde cellulose nanofibers and the aldehyde cellulose nanosheets extend freely; and wherein the amino biopolymer, the hydroformylated cellulose nanofiber, the hydroformylated cellulose nanosheet and the hydroformylated lignin form a cross-linked network by hydrogen bonding and covalent binding. The invention further provides a method for preparing the surface aldehyde bamboo powder composite material.

The invention discloses a magnetic composite material for detecting a flavone compound, a preparation method, a detection method and an application in preparation of a standard substance, and belongs to the technical field of analytical chemistry. The magnetic composite material comprises a magnetic nanoparticle core, a first shell layer of a double-lanthanide metal organic framework (MOF) and a second shell layer of a covalent organic framework (COF) which are sequentially coated on the surface of the magnetic nanoparticle core, and a phenylboronic acid group grafted on the surface of the second shell layer. According to the material, high-efficiency capture and enrichment are realized by utilizing specific covalent binding of phenylboronic acid and characteristic catechol hydroxyl of a flavone compound; the double-lanthanide MOF shell layer promotes energy transfer, the COF shell layer provides a high specific surface area and an ordered diffusion channel, and the magnetic core is convenient for rapid separation, so that high-selectivity recognition of flavone compounds is jointly realized. The material has the advantages of high sensitivity, strong matrix interference resistance, rapidness, simplicity and convenience in detection and the like, and is suitable for accurate analysis of flavone compounds in complex samples and development of related standard substances.

Disclosed herein are EphA2 targeting compounds or pharmaceutically acceptable salt or radioactive metal complex thereof, and methods of their use in the treatment of EphA2 positive cancer. In certain embodiments, the compound is a Targefrin monomer or dimer compound complexed with a radiometal, such as lutetium-177. In certain embodiments, the compound is an irreversible covalent binder of EphA2. In certain embodiments, the compound is a cyclic compound.

The application discloses a natural fissistilarin component derivative DhpB and application thereof, and particularly application thereof as a covalent binding ubiquitinase MKRN2 target in anti-KRAS mutant lung cancer. The derivative is from a plant of Peperomia in Piperaceae, can significantly inhibit in-vivo and in-vitro proliferation of KRAS mutant non-small cell lung cancer cells, and induce tumor cell apoptosis through semi-synthetic structure optimization. DhpB is covalently combined with ubiquitinase MKRN2 abnormally expressed in KRAS mutant lung cancer cells, promotes combination of MKRN2 and small ribosomal protein RPS7, thereby promoting ubiquitination and degradation of RPS7, and causes ribosome stress-induced apoptosis of tumor cells. The application provides a new target and inhibitor for preparing a drug for treating refractory KRAS mutant lung cancer, and has a good medicinal prospect.

This invention provides a detection method for distinguishing between live and dead bacteria of the watermelon fruit spot bacterial disease fungus. [Solution] A detection method for distinguishing between live and dead bacteria based on PMA-PCR technology, comprising: a step of collecting and suspending bacteria in a sample to be detected, which involves suspending the sample in physiological saline to obtain a bacterial suspension and heating it in a 100°C water bath for 10 minutes to prepare a dead bacterial suspension; a step of PMA treatment, which involves adding propidium monoazide (PMA) to the bacterial suspension; a step of blue light crosslinking, which involves irradiating the PMA-treated bacterial suspension with blue light to activate the PMA and covalently bind it to the dead bacterial DNA; a step of DNA extraction, which involves collecting bacterial cells by centrifugation and extracting DNA using a kit method; a PCR amplification step, which involves amplification using a specific primer pair; and a step of detecting the amplified product by agarose gel electrophoresis, which involves determining the result, which involves a step of detecting the product by agarose gel electrophoresis, wherein a target band appears in the live bacterial sample and no band appears in the dead bacterial sample.

The present invention relates to a method for forming a conjugate of a desired target substance and a peptide. A method according to the present invention includes a step for bringing a genetic information material-linker-peptide conjugate into contact with a target substance conjugate containing at least two target substances. The genetic information material-linker-peptide conjugate includes: (a) a linker that includes a bond portion having a structure capable of binding to a desired genetic information material and includes at least two puromycin-like substances, the puromycin-like substances being capable of covalently binding to the C-terminus of a desired peptide; (b) a genetic information material that is bonded to the bond portion of the linker of (a); and (c) a peptide that is bonded to at least two or more puromycin-like substances of the linker of (a) and is encoded by the genetic information material.

A method for extracting at least 55% of immunoglobulin such as IgG from a biological fluid. The biological fluid containing immunoglobulin is contacted with a solid support covalently bonded to a ligand that specifically binds to immunoglobulin under conditions sufficient for non-covalent binding of immunoglobulin to the ligand. The solid support is contacted with an elution solution under conditions whereby the non-covalently bound immunoglobulin is released from the ligand and into the elution solution, wherein at least 55% of the IgG present in the biological fluid is extracted into the elution solution. The method, in some embodiments, provides a method for enriching immunoglobulin from a biological fluid comprising obtaining an initial biological fluid suspected of containing immunoglobulin and removing non-immunoglobulin components naturally occurring in the initial biological fluid to obtain a non-immunoglobulin component-reduced biological fluid.

This invention relates to a class of activation-triggered in-situ anchored mitochondrial-targeted fluorescent probes for peroxynitrite anions and their applications. Specifically, the probes of this invention exhibit excellent detection performance for peroxynitrite anions in a pure water system. This is mainly manifested in: achieving precise quantitative detection of ONOOˉ in mitochondria, with significant changes in the fluorescence spectrum generated by the reaction between the probe and ONOOˉ; possessing high selectivity, enabling highly selective detection of ONOOˉ in complex biological environments, with response intensity and speed exceeding those of other analytes; rapid reaction and high sensitivity, with a low detection limit for ONOOˉ; simultaneously, it can respond in a pure water system, making it environmentally friendly; most importantly, this probe can detect peroxynitrite anions in mitochondria and achieve long-term in-situ tracer imaging through covalent binding.

The invention discloses a persimmon tannin modified bio-based composite adsorption material and a preparation method thereof, and belongs to the technical field of water pollution treatment, metal element loading and bio-based materials. The preparation comprises aminated persimmon tannin and aldehyde cellulose. Persimmon tannin is subjected to amination modification to introduce amino groups, cellulose is subjected to oxidation modification to generate aldehyde groups, the amino groups and the aldehyde groups react in a weak acid environment to form imine bonds and generate covalent binding, the persimmon tannin is anchored on a cellulose porous framework, and the problem that the persimmon tannin is lost along with water flow in the adsorption process of water treatment is avoided; and in the adsorption process, metal ions and organic matters in the water body can be captured through chelating of phenolic hydroxyl groups in persimmon tannin. In addition, the porous structure of the cellulose contains a large number of adsorption active sites, and the contact probability of the active sites is increased, so that the adsorption efficiency is effectively improved.