27 results about "Molecular stability" patented technology

The invention provides deuterated aza-adenine and a preparation method and application thereof.The deuterated aza-adenine has the structure shown in the formula (I), the deuterated aza-adenine compound can improve the molecular stability, the copper surface binding force of a product is improved when the deuterated aza-adenine compound is applied to a photosensitive composition, and the yield of the product is improved. And other application performances of the molecules are not influenced.

The invention relates to the field of electroporation, and provides an electroporation regulation and control method for exosome-loaded miRNA in order to solve the aggregation problem after electroporation and determine the optimal electroporation condition to improve the loading efficiency and the molecular stability, and the method comprises the following steps: S100, obtaining the relationship among the concentration of a to-be-detected substance, a pulse parameter and an aggregation parameter of the to-be-detected substance; the aggregation parameters comprise an aggregation speed and an aggregation rate; the to-be-detected object comprises an exosome and miRNA (micro Ribonucleic Acid); and S200, selecting the concentration and pulse parameters of the to-be-detected object corresponding to the aggregation rate less than the first preset value and the aggregation speed greater than the second preset value as the actually used electrical conversion parameters. According to the invention, the concentration of the to-be-detected object and the pulse parameter are continuously adjusted by detecting the aggregation parameter so as to obtain the optimal electrical conversion parameter, so that in the electroporation process, the optimal electrical conversion parameter is obtained through the migration condition and the aggregation condition, and the to-be-detected object has a certain migration rate and a relatively low aggregation rate; meanwhile, aggregation of the exosome is reduced, and the recovery rate of the exosome is increased.

The invention discloses a dual-mode sensor based on a histamine aptamer H32 and application of the dual-mode sensor, and belongs to the technical field of food safety analysis and detection. The aptamer as shown in SEQ ID NO.1 is used as a recognition molecule of histamine, the stability is high, the preparation cost is low, and the aptamer has high affinity and high selectivity to histamine. According to the invention, dual-mode signal complementation is realized, ultraviolet and fluorescent dual channels cover a wide dynamic range of 3-30 [mu] M, the detection range is expanded compared with a single-mode detection range, and detection can be rapidly completed. The construction of the sensor provides a choice for aquatic product safety monitoring, and has certain application potential in the fields of aquatic product monitoring and food quality control.

The invention relates to the technical field of biomedical materials, in particular to polynucleotide / macromolecular protein composite gel capable of tolerating terminal moist heat sterilization as well as a preparation method and application of the polynucleotide / macromolecular protein composite gel. The product provided by the invention is a composite gel of polynucleotide PN and a specific type of high-molecular protein, and under the conditions of a specific ratio and molecular weight, the high-thermal denaturation temperature is higher, and the high-molecular protein with a specific structure has a better protection effect on the polynucleotide PN; the stability and biological activity of polynucleotide PN molecules can be kept under the condition of high-temperature terminal sterilization, the safety of a sterilized product can achieve the effect of thoroughly inactivating viruses, and the filling and supporting properties of the product serving as a stent material are completely reserved; the compound can be directly used in drugs, medical instruments or cosmetics in the field of tissue engineering, and has high safety and lasting effect.

The invention provides a bifunctional fusion protein radionuclide marker with a brand new structure model, which has higher labeling rate and radiochemical purity, keeps higher affinity and functional activity, and has proper molecular weight, strong tissue penetrability, good imaging effect, proper cycle half-life period and strong molecular stability. After a target carrier is radiolabeled, the target carrier still shows good affinity and is not affected, has good biological metabolic activity and clearance rate, has the effects of reducing radiation toxicity, kidney toxicity, blood toxicity and non-target organ toxicity, is well enriched in tumor cells, is beneficial to realizing diagnosis and accurate staging of tumor focuses, and can be used as a target carrier to improve the clinical application prospect. Precise radiotherapy of primary focuses and metastatic focuses is achieved, good safety and effectiveness potential are achieved, and good application prospects are achieved in the field of solid tumor treatment.

The present invention relates to RNA molecules, and particularly, although not exclusively, to unlocked nucleotides (UNAs) and unlocked nucleic acid (UNA)-RNA molecules per se, to methods for preparing UNA-RNA molecules, and to methods for translating UNA-RNA molecules into protein. The invention extends to improved methods for forming UNA-RNA by in vitro transcription, and to the resultant UNA-RNA molecules. Furthermore, the invention relates to novel methods for enhancing the expression and / or translation of RNA, i.e. protein expression, and to methods for improving the stability of an RNA molecule. The invention also involves reducing the activation of innate sensing, interferon generation and / or degradation of an RNA molecule in a host. The invention also incorporates the use of the UNA-RNA molecules in vaccines and other therapeutic pharmaceutical compositions, and their use in immunisation and therapy, such as RNAi, gene therapy, gene editing and protein replacement. Furthermore, the invention relates to novel methods for enhancing translation of RNA, i.e. protein expression.

The invention belongs to the field of drug preparation and drug delivery, and particularly relates to a metal compound capable of improving stability and a preparation method and application thereof. A pyridine group is introduced on the basis of the BODIPY diplatinum ligand F1, the conjugation characteristic of the pyridine group can enhance the molecular stability of the metal ring, and the electron-withdrawing characteristic of the pyridine group is also beneficial to enhancing the light absorption capacity of the metal ring.

The compounds have been developed and synthetically disclosed to produce compounds that improve film applications, such as HfOx, ZrOx, and TiOx film applications. The improvements in compounds of the present disclosure include improvements relating to increased molecular stability at delivery and deposition temperatures, precursor film impurity levels, molecular volatility, molecular melting point, and step coverage.

The invention discloses a three-dimensional molecular structure aided design method based on a neural network and text description. After a reference data set is constructed, a text-2D structure alignment model used for aligning text description and a two-dimensional molecular graph, a 2D-3D noise structure alignment model used for aligning the two-dimensional molecular graph and a three-dimensional molecular graph and a prior model used for converting the text description into the two-dimensional molecular graph are sequentially trained; through training the conditional diffusion model, the isodenaturation of the three-dimensional molecular structure on translation, rotation, reflection and arrangement is maintained, and through the trained contrast learning model and the trained conditional diffusion model, based on the mean shift of text gradient guide conditional diffusion model sampling, the three-dimensional molecular structure which has expected properties and accords with text description is generated. And after post-processing, the aided design is completed. According to the method, the three-dimensional molecular structure is generated from the beginning of text description, and compared with the prior art, the chemical effectiveness, atomic stability and molecular stability indexes of generated three-dimensional molecules are improved.

The present invention provides a modified protein sequence, namely a recombinantly expressed glycan-binding protein. This glycan-binding protein is a variant of the Sclerotium Rolfsii lectin and has been modified to include features such as increased molecular stability, a reduction in N-terminal methionine impurities, and improved protein conjugation with other biological and chemical agents.

The invention belongs to the technical field of biology, and particularly relates to a liver microsome compound stability prediction method based on a deep neural network, which comprises the following steps: acquiring liver microsome compound molecule data, and representing each liver microsome compound molecule as a corresponding SMILES character string; character group-to-ID processing is carried out on the liver microsome compound molecule data to obtain matrix vector data; constructing a deep neural network model; training a deep neural network model by adopting matrix vector data, calculating loss and carrying out back propagation to train model parameters; and predicting the stability of the liver microsome compound by adopting the trained deep neural network model. According to the invention, high-precision molecular stability prediction can be carried out.

This invention relates to the technology of antibodies, and more specifically, to antibodies that bind to the IL-18 receptor, IL-18 receptor activators, and their use. The invention provides antibodies that specifically bind to IL-18R1 and IL-18RAP with high affinity, and further provides bispecific antibodies that can efficiently bind both IL-18R1 and IL-18RAP simultaneously. These bispecific antibodies are novel IL-18 receptor activators that can activate the intracellular signaling pathway mediated by IL-18R1 / IL-18RAP, exert biological functions similar to IL-18 both in vitro and in vivo, and possess broad immunostimulatory effects and remarkable antitumor activity. Furthermore, they possess controllable activating activity, excellent molecular stability, and in vivo pharmacokinetic characteristics, which are advantageous for fully exhibiting antitumor efficacy in vivo, and offer prospects for a wide range of antitumor clinical applications.

The invention relates to the technical field of chemistry, in particular to a tyrosinase inhibitor and application thereof, and the tyrosinase inhibitor comprises a compound with the structure shown in the specification or physiologically acceptable salt of the compound. The tyrosinase inhibitor provided by the invention has remarkable tyrosinase inhibition activity, can effectively block melanin synthesis, and is small in toxic and side effects and high in molecular stability.

The invention discloses a synergistic treatment method for improving the stability of three-type collagen, and belongs to the technical field of stability regulation and control of biomacromolecules. The method comprises the following steps: dissolving purified type III collagen in a buffer solution, and stirring until the type III collagen is completely dissolved; adjusting the pH value of the collagen solution to 5.5-6.5 by using a pH regulator, adding a composite protective agent into the collagen solution with the adjusted pH value, stirring until the collagen solution is completely dissolved, and then carrying out temperature gradient treatment to obtain a type III collagen solution subjected to temperature gradient treatment; and storing the type III collagen solution subjected to temperature gradient treatment under the condition that the temperature is 20-30 DEG C. Through the synergistic effect of pH regulation and control, addition of the composite protective agent and temperature gradient treatment, the structural stability of the type III collagen can be remarkably improved, and the effective preservation period of the type III collagen can be prolonged.

The invention belongs to the technical field of protein engineering modification, and particularly relates to an assembled cyclopeptide immobilized protease variant based on molecular dynamics calculation. In order to improve the structure and performance of the protease, cyclopeptide covalent assembly calculation simulation is carried out on the protease structure with the distance between an N-terminal alpha amino group and a C-terminal alpha carboxyl group being between # imgabs0 #, and through molecular dynamics calculation, by taking reduction of the turning radius of the protease and the accessible area of a solvent as a benchmark, the content of the protease in the protease is reduced. And finding the position and chain length structure of the covalent binding fusion connection short polypeptide with the greatest contribution to the protease molecular stability to obtain the stably assembled cyclopeptide alkaline protease variant of # imgabs2 # with the turning radius reduced than that of the original parent protease # imgabs1 # and the accessible area reduced than that of the original parent protease # imgabs2 #.

The invention provides a thermal acid generator and a preparation method and application thereof.The thermal acid generator has the structure shown in the formula (I), the thermal acid generator can improve the molecular stability, and when the thermal acid generator is used in a thermocuring composition, initiation activity can be kept under the condition that other formula components do not need to be changed, the stability of a product is improved, and the thermal acid generator can be applied to the thermocuring composition. And the curing speed is kept unchanged.

The present disclosure generally relates to stable synthetic RNA molecules and to methods of producing such stable synthetic RNA molecules. Also, the present disclosure generally relates to methods for determining the stability of RNA molecules. In some aspects, the methods described herein can enhance design and synthesis of RNA-based therapeutics.

This invention relates to the field of chemical technology, and more particularly to a tyrosinase inhibitor and its application. The tyrosinase inhibitor comprises a compound having the structure shown or a physiologically acceptable salt thereof. The tyrosinase inhibitor provided by this invention exhibits significant tyrosinase inhibitory activity, effectively blocks melanin synthesis, and has low toxicity and high molecular stability.

The present invention relates to RNA molecules, methods for preparing RNA molecules, and methods for translating RNA molecules into proteins. The present invention extends to improved methods for forming RNA by in vitro transcription, and the resulting RNA molecules. Furthermore, the present invention relates to novel methods for improving RNA expression and / or translation, i.e., protein expression, and methods for improving the stability of RNA molecules. The present invention also includes reducing the activation of innate sensing, interferon production, and / or degradation of RNA molecules in a host. The present invention also incorporates the use of RNA molecules in vaccines and other therapeutic pharmaceutical compositions, and their use in immunization and therapy, such as RNAi, gene therapy, gene editing, and protein replacement.

The invention relates to the technical field of biological medicines, in particular to an Fc-hGH fusion protein, coding nucleic acid, a carrier, an engineering cell as well as a construction and preparation method and application of the Fc-hGH fusion protein. From an N terminal to a C terminal, the Fc-hGH fusion protein comprises hGH and an IgG4 Fc mutant which are connected in sequence; compared with a wild type IgG4 Fc, the IgG4 Fc mutant has the following mutations: F234A, L235A, M428L and N434S. The invention also discloses a preparation method of the IgG4 Fc mutant. The Fc fragment variant of the IgG4 and the growth hormone form the fusion protein, and through the design of the Fc fragment variant of the IgG4, the ADCC effect, the ADCP effect and the CDC effect caused by the combination of an Fc region and Fc gamma R are eliminated, the in-vivo distribution of the drug is changed, the in-vivo half-life period of the drug is prolonged, and the molecular stability can be improved.

Provided in the present invention is a bifunctional fusion protein radionuclide label, which has a high labeling yield and high radiochemical purity while maintaining high affinity and high functional activity, and has a suitable molecular weight, strong tissue penetration, a good imaging effect, a suitable circulation half-life, and strong molecular stability; the bifunctional fusion protein radionuclide label still has good affinity without being affected after radiolabeling a targeting carrier, has good biological metabolic activity and a good removal rate, and has reduced radiation toxicity, renal toxicity, hematological toxicity, and non-target organ toxicity; the bifunctional fusion protein radionuclide label has good enrichment in tumor cells, is conducive to implementing diagnosis and accurate staging of tumor lesions, and serves as a targeting carrier for implementing precision radiotherapy on primary lesions and metastatic lesions; and the bifunctional fusion protein radionuclide label has good safety and effectiveness potential, and has good application prospects in the field of solid tumor treatment.

The application relates to a preparation and application of an FXI targeting siRNA molecule and a GalNAC conjugate thereof. The siRNA molecule takes TN7 sequence as a core, is obtained through precise bioinformatics design and high-throughput screening, and has excellent gene silencing activity. Through systematic chemical modification optimization, the stability of the molecule is significantly improved. More importantly, the TN7-GalNAC conjugate exhibits an unprecedented persistent inhibitory effect in a mouse in-vivo experiment, and the FXI protein level is maintained below 10% of the basic level within 28 days after single administration. The application provides a new molecular tool for precise treatment of thrombotic diseases, and has important clinical application value.

The invention relates to an engineered cell for heterologous co-expression in escherichia coli and a construction method of the engineered cell, and belongs to the technical field of microorganisms. The construction method comprises the following steps: (1) constructing a fusion gene; (2) performing escherichia coli preference codon optimization; (3) constructing a recombinant plasmid pET-28a-EHb and a recombinant plasmid pET-28a-EMb, and constructing a recombinant plasmid pET-28a-EHb; (4) carrying out PCR (Polymerase Chain Reaction) amplification to obtain an HbF fusion gene segment and an Mb gene segment; (5) constructing a co-expression fragment through fusion PCR; (6) constructing a co-expression recombinant plasmid; and (7) transforming the co-expression recombinant plasmid into an escherichia coli host cell, and culturing to obtain an engineered cell for heterologous co-expression in escherichia coli. The invention constructs a co-expression system based on fetal hemoglobin and fetal myoglobin, and obtains a recombinant heme protein composition with oxygen binding performance, molecular stability and high expression efficiency.

The invention belongs to the field of biological pharmacy, and provides a preparation method and application of a CircILNb molecule co-expressing an IL-15 and anti-PD-L1 nano antibody, and the CircILNb molecule comprises the following sequences: a CVB3IRES sequence, an anti-PD-L1 nano antibody coding sequence, an IL-15 coding sequence and a connection sequence. The CircILNb molecule provided by the invention is a circular RNA molecule synthesized and purified in vitro, is good in stability, high in purity and low in immunogenicity, can simultaneously secrete and express IL-15 and anti-PD-L1 nano antibodies in cells after being packaged, can simultaneously secrete and express the IL-15 and anti-PD-L1 nano antibodies after being packaged and injected into a human body, and can be used for preparing a medicine for preventing and treating the IL-15 and anti-PD-L1 nano antibodies. And immune cells are activated while tumor cells are inhibited.

The invention belongs to the field of computational biology and protein engineering, and discloses a cross-species universal paramyxovirus RdRp design method and system, the design system fuses multi-level information such as sequences, protein language characterization and structures, an RdRp candidate sequence with a cross-species function is mined through a multi-mode and multi-model cooperation strategy, and the cross-species universal paramyxovirus RdRp is obtained. The method mainly comprises a candidate mining stage, a preliminary design and wet experiment verification stage and a structure optimization stage, BLAST and other methods are used for sequence similarity analysis, deep representation of a protein sequence is extracted in combination with ESMC and other protein language models, three-dimensional structure prediction is carried out with the assistance of Alphafold3, and the three-dimensional structure is obtained. RdRp candidate molecules with a potential cross-species universality function are screened out by combining multi-dimensional similarity indexes, after preliminary design, structural correction and optimization are performed by means of a protein generation model such as RFdiffusion, and the molecular stability, universality and target binding capacity of the RdRp candidate molecules are emphatically improved.

The invention belongs to the technical field of biological medicine detection, and provides a fluorescent probe as well as a preparation method and application thereof. The fluorescent probe disclosed by the invention can emit relatively weak fluorescence and also can specifically and rapidly react with the ALDH2 enzyme to generate a product with strong fluorescence, and the fluorescence intensity is positively correlated with the concentration of the ALDH2 enzyme. The fluorescent probe has the beneficial effects that (1) the fluorescent probe used for detecting the enzyme activity of ALDH2 is good in molecular stability and can be stored and used for a long time; and (2) the fluorescent signal brightness is high, the detection signal-to-noise ratio is high, and the sensitivity is good. (3) the selectivity is excellent, and ALDH2 enzyme can be specifically detected in a complex biological sample. And (4) good biological membrane permeability is achieved, so that the method can be used for detecting the enzyme activity of ALDH2 in living cells. And (5) the detection speed is high. And (6) the detection response is sensitive, and the signal intensity can be enhanced along with the increase of the ALDH2 enzyme content in the species to be detected.

The present invention provides a compound comprising X having at least one hydroxyl group, wherein at least one hydroxyl group is independently substituted by one or more ‑Y‑Z groups, or a stereoisomer, geometric isomer, tautomer, nitrogen oxide, hydrate, solvate, metabolite, or pharmaceutically acceptable salt thereof; X is selected from grifolin or an analog thereof, Y is a linking group, and Z is a solubilizing group. The compound of the present invention is a Grifolin molecular prodrug with good water solubility. After administration, the original drug is slowly released in plasma, stabilizing the bisphenol structure of Grifolin and improving molecular stability. It can effectively inhibit DNMT1 gene expression, thereby contributing to a good anti-cancer effect. The compound provides scientific research value and clinical application value for the study of the DNMT1 gene and the treatment of cancer, and is of great significance.