20 results about "Enzyme degradation" patented technology

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 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 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 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 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 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.

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.

The invention discloses synthesis of phosphamide derived from 3-sulfydryl nucleotide and application of the phosphamide to oligonucleotide. The phosphamide modified oligonucleotide comprises nucleotide structural units shown as a formula I or a formula II,..., the formula I,..., the formula II. Through specific limitation of a nucleotide phosphamide monomer structure, the prepared oligonucleotide comprises a phosphamide structural unit derived from 3-mercaptonucleotide; compared with the traditional oligonucleotide molecule, the phosphamide modified oligonucleotide molecule of 3-mercapto nucleotide shows better enzymatic degradation resistance and pharmaceutical stability. In addition, the phosphamide modification of the 3-mercapto nucleotide can improve the binding performance between the modified oligonucleotide molecules and environmental ions, and a novel chemical modification strategy is provided for research, development and application of oligonucleotide drugs.

The invention discloses synthesis of phosphoramide derived from 5-mercapto nucleotide and application of the phosphoramide to oligonucleotide. The phosphoramide modified oligonucleotide comprises nucleotide structural units shown as a formula I or a formula II,..., the formula I,..., the formula II. Through specific limitation of a nucleotide phosphamide monomer structure, the prepared oligonucleotide comprises a phosphamide structural unit derived from 5-mercaptonucleotide. Compared with the traditional oligonucleotide molecule, the phosphamide modified oligonucleotide molecule of 5-mercapto nucleotide shows better enzymatic degradation resistance and pharmaceutical stability. In addition, phosphoramide modification of 5-mercapto nucleotide can improve the binding performance between modified oligonucleotide molecules and environmental ions, and a novel chemical modification strategy is provided for research, development and application of oligonucleotide drugs.

The invention relates to the technical field of biological medicine, and particularly discloses synthesis and application of 5-terminal thiophosphorylation modified oligonucleotide. The nucleotide C5 is connected with the thiophosphoric acid through a carbon-thiophosphoric acid chemical bond; the chemical modification strategy comprises the following steps: preparing nucleotide phosphoramidite which is connected between the C5'and the thiophosphoric acid through the carbon-thiophosphoric acid chemical bond; performing solid-phase synthesis on the phosphoramidite monomer for modifying the nucleotide to construct a target oligonucleotide molecule; the 5 '-terminal of the oligonucleotide is connected with the thiophosphoric acid through a carbon-thiophosphoric acid C-PSO22-chemical bond to form a non-natural 5'-terminal thiophosphoric acid structure which does not belong to a natural substrate of phosphatase, and the modified oligonucleotide can resist the degradation of exonuclease and can improve the biological activity of a nucleic acid drug in a living body.

The invention relates to a rapid high-throughput capping efficiency detection method and application thereof in screening UTR (Untranslated Region) sequences, in particular to mRNA (Messenger Ribonucleic Acid) efficient expression UTR sequence design and rapid high-throughput detection of capping efficiency and poly (A) integrity, and the UTR sequences comprise 5 'UTR and Poly (A) sequence parts. The 5 'UTR is divided into a sequence A and a sequence B in the 5'-3 'direction, the sequence A is composed of 9-42 nt basic groups A or G, the last basic group is C or U, the secondary structure of the sequence A is simple, RNaseA enzyme degradation can be resisted, and efficient capping and rapid high-throughput mRNA capping efficiency detection can be achieved at the same time; the B region sequence is an artificially designed sequence and / or a chimeric sequence containing a 18s rRNA complementary sequence. The Poly (A) sequence is composed of a plurality of AmGn sequences, m is larger than 30, n is equal to 1, 2, 3, 4 and the like, the Poly (A) sequence can resist RNase A enzymatic degradation, and the length integrity of the Poly (A) can be rapidly detected in a high-throughput mode.

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

Disclosed herein are an enzyme capable of degrading a highly recalcitrant plastic or a variant thereof, a composition comprising the same, and a method of degrading a highly recalcitrant plastic using the same. In addition, according to the present disclosure, polyethylene (PE) as a highly recalcitrant plastic can be effectively degraded as well as oxidized PE, which can be useful for developing plastic waste treatment and upcycling of plastic waste.