54results about How to "Improve specific binding ability" patented technology

Provided are siRNA molecules of between about 15 base-pairs and about 40 base-pairs comprising one or more universal-binding nucleotide such as inosine, 1-β-D-ribofuranosyl-5-nitroindole, and 1-β-D-ribofuranosyl-3-nitropyrrole, compositions comprising one or more universal-binding nucleotide comprising siRNA, and methods for making and for using such universal-binding nucleotide comprising siRNA molecules to increase the specific binding of the modified siRNA molecule to variants of a target sequence such as, for example, when in contact with a biological sample and to reduce off-target effects of the siRNA molecule.

The invention relates to an injection anticancer long circulating targeting liposome which is characterized in that anti-angiogenic drug is combined with anticancer drug, the liposome modified by polypeptide with tumor targeting function and hydrophilic polyethyleneglycol is adopted for loading and transporting the two drugs to tumor positions, and the tumor curative effect is enhanced through the different releasing rates and action mechanism of the two drugs.

The invention discloses a novel single-domain antibody resistant to human beta2-microglobulin as well as a preparation method and an application of the single-domain antibody. A phage display technology is adopted to perform multiple rounds of screening on an alpaca phage antibody library to obtain phage enriched with beta2-microglobulin specificity, the phage is cultured for preparing the antibody, positive clone is obtained through identification, a coding sequence corresponding to the positive clone is obtained through sequencing, and then expression is performed in escherichia coli to obtain a soluble antibody fragment. The antibody has an amino acid sequence represented as SEQ ID NO.1 or SEQ ID NO.10. The antibody provided by the invention has very high bonding capacity for beta2-microglobulin, can be applied to the fields of blood purification and beta2-microglobulin detection, and facilitates promotion and improvement of diagnosis and treatment for diseases such as dialysis-related amyloidosis and the like.

The invention discloses a preparation method for a magnolol molecularly imprinted polymer film. The preparation method includes the following concrete steps: both imprinted molecule magnolol and solid-phase reagent are put into a ball mill and ball-milled, so that imprinted molecule inclusion compound is obtained, and the inclusion compound, functional monomer, cross-linking agent and initiator are put into porogen, ultrasonically degasified, then added with bond and ultrasonically stirred, so that mixture is obtained; filter paper is immersed in the mixture, taken out, clamped between two glass sheets, put into an oven and heated to be polymerized, so that polymer is obtained; imprinted molecules are removed from the obtained polymer, and after washing and drying, the magnolol molecularly imprinted polymer film is obtained. The preparation method adopts the mechanochemical technology to include the imprinted molecules, so that the ability of the imprinted molecules in specific binding with the functional monomer is enhanced, as a result, the recognition selectivity of the finally prepared molecularly imprinted polymer film is greatly enhanced, and the magnolol separation effect is good.

The invention discloses salicylanilide derivatives, which have the following general formula, wherein R1 is H or Br; R2 is H or Br; R3 is H or CH3; R4 is F, Cl, Br or I; R5 is F, Cl, Br or I; and R6 is CH3, OCH3, CH(CH3)2 or halogen. The salicylanilide derivatives have obvious inhibiting effect on HEP-G2 and EGFR in liver cancer cells, so the salicylanilide derivatives can be applied in preparing a medicament against liver cancer. The invention discloses a preparation method for the salicylanilide derivatives.

The invention belongs to the technical field of monoclonal antibodies, and particularly discloses a new coronavirus RBD specific monoclonal antibody and application thereof. The new coronavirus RBD specific monoclonal antibody has the important scientific significance and application prospect for prevention and clinical treatment of diseases caused by the new coronavirus SARS-CoV-2 and research and development of diagnostic reagents.

The invention relates to a preparing method of a nanometer polymer micelle carrier integrating diagnosis and treatment. The method includes following steps of: (1) dissolving 0.1-1 part by weight of a hydrophobic anticancer medicine, 1-10 parts by weight of a magnetic resonance sensitive molecular probe, 4-40 parts by weight of polyethylene glycol-polycaprolactone end-capped with methoxy, 0.8-8 parts by weight of a polymer micelle with an active targeting group and 0.8-8 parts by weight of FITC-PEG-PCL into 1-100 parts by weight of tetrahydrofuran to obtain a mixture; (2) adding the mixture prepared in the step (1) into 5-800 parts by weight of deionized water, dialyzing and volatilizing to remove the organic solvent to obtain a targeted FA-NP / SPIO / PTX nanometer polymer micelle; and (3) subjecting the targeted FA-NP / SPIO / PTX nanometer polymer micelle prepared in the step (2) to filter membrane filtration and centrifugation to remove the unloaded or uncovered antitumor medicine so as to prepare the nanometer polymer micelle carrier integrating diagnosis and treatment, wherein the inner core of carrier carries the hydrophobic medicine and the magnetic resonance sensitive molecular probe, and the outer shell of the carrier is provided with the active targeting group.

The invention discloses weight-losing / weight-controlling absorbable jelly and a preparation method thereof, relates to the technical field of food processing, and fills he technical blank that no absorbable jelly prepared by a cold process exists in the prior art. The absorbable jelly comprises the following raw materials in parts by weight: 0.5 to 1.5 parts of calcium alginate, 0.5-1 part of potassium carbonate, 1-2 parts of a calcium-releasing freezing agent, 0.1-8 parts of heat-sensitive weight-losing and weight-controlling powder, 2-30 parts of L-arabinose, 0.1-3 parts of an agaricus bisporus extract, 1-5 parts of fruit powder, 0.01-0.06 part of potassium sorbate, 0.1-0.5 part of citric acid, 0.1-0.5 part of sodium citrate and the like. The heat-sensitive weight-losing and weight-controlling powder is one or a composition of white kidney bean extract, seaweed ferment powder, potato extract and fish collagen powder. The absorbable jelly disclosed by the invention is developed from functional food raw materials, is a safe food with weight losing and weight controlling effects, and has a good market prospect.

The invention provides an antibody or fragment thereof that binds to human tumor-associated calcium signal transducer 2 (Trop-2) protein, and an application of the antibody or fragment thereof to prevention or treatment of diseases. The antibody or the fragment thereof can be effectively combined with the human Trop-2 protein, has internalization activity, is enhanced in internalization activity after ADC drug labeling, and is not lower than a control antibody in in-vivo drug effect and safety of a mouse model.

The invention provides 5-fluorouracil derivatives, 5-fluorouracil immunogens, antibody for the immunogens, and a 5-fluorouracil detection kit. The 5-fluorouracil derivatives provided by the invention have a structure shown in a formula (I) as shown in the specification, wherein R is -(CH2)n-COO- and n is an integer between 1 and 20. The 5-fluorouracil derivatives with the structural formula are combined with a specific carrier, so that the prepared 5-fluorouracil immunogens have high immunogenicity; and the antibodies generated by an animal immunized with the immunogens have relatively high sensitivity and specificity, and have high specific combining ability with 5-fluorouracil. Through use of a homogeneous enzyme immune detection technology, high-flux and fast detection of 5-fluorouracil by an full automatic biochemical analyzer can be achieved; and the detection is convenient to operate, high in sensitivity, high in specificity, accurate in result and the like; the 5-fluorouracil detection cost can be effectively reduced; and clinical promotion and application are facilitated.

The invention belongs to the field of molecular biology, and particularly relates to an EpCAM single domain antibody G7 and a nucleotide sequence for encoding the EpCAM single domain antibody G7. By utilizing a phage display technology, a single domain heavy chain antibody library specifically bound with a target antigen CD326 is screened from a camel-source immunizing single domain heavy chain antibody library, and a coding sequence of a positive clone is further guided into a prokaryotic expression vector, so that the high-efficiently expressed EpCAM single domain antibody G7 is obtained. Therefore, a basis is provided for clinic targeted immunological therapy of CD326.

The invention relates to an anticancer genetic engineering bivalent antibody, a preparation method thereof, and an anticancer genetic engineering drug. The anticancer genetic engineering bivalent antibody comprises a constant region, and SIRPa and B7 connected with the constant region. The preparation method of the anticancer genetic engineering bivalent antibody comprises following steps: acquirement of constant region gene, SIRPa gene, and B7 gene; construction of an expression plasmid containing the three genes; transfection of the expression plasmid into expression cell strain for culturing; and obtaining of the bivalent antibody via separation and purification. The bivalent antibody comprises both SIRPa and B7 which are capable of realizing specific binding with CD47 locus of tumor cells and CD28 locus of lymphocyte; specific binding performance is improved greatly; double inhibition on body tumor cells is realized; the preparation method is simple and practicable; tumor cells can be influenced by the anticancer genetic engineering drug containing the anticancer genetic engineering bivalent antibody effectively; and the anticancer genetic engineering drug is capable of preventing and treating tumor diseases effectively.

The invention provides a creatinine derivative, a creatinine immunogen and a specific antibody as well as a creatinine detection kit. The creatinine derivative has a structure represented by the formula (I) as shown in the description, wherein R is -(CH2)n-COO- and n is an integer from 1 to 20. The creatinine immunogen, which is obtained by linking the creatinine derivative of which H on the specific site is substituted by R and which has the above formula and a specific carrier, has high immunogenicity, the antibody produced by immunizing and inducing animals is high in specificity and has strong specific binding capability with the creatinine; the high-throughput and rapid detection of creatinine can be achieved by virtue of a homogeneous enzyme immunoassay technology on a full-automatic biochemistry analyzer, the method has the advantages of high sensitivity, strong specificity and accurate results and is simple and convenient to operate, the creatinine detection cost can be effectively decreased and the method is conductive to clinical popularization and application.

The invention relates to an anti-HIV gene engineering recombinant virus and a preparation method thereof, and an anti-HIV gene engineering medicament. The anti-HIV gene engineering recombinant virus comprises a constant region of a human antibody, and a cluster of differentiation 4 (CD4) and a chemokine receptor 5 (CCR5) which are connected with the constant region. The preparation method for the anti-HIV gene engineering recombinant virus comprises the steps as follows: obtaining a heavy chain constant region gene of the human antibody, a light chain constant region gene of the human antibody, a CD4 gene and a CCR5 gene; constructing a virus vector shuttle plasmid comprising the four genes; co-transforming the shuttle plasmid and a virus auxiliary plasmid to generate a recombinant virus plasmid; and transferring the recombinant virus plasmid to a cell strain for culturing and purifying the virus. The recombinant virus has both the CD4 and CCR5 capable of specifically binding with the CD4 site and CCR5 site of an HIV virus, an obviously enforced specific binding effect, and the function of doubly preventing the HIV virus from infecting a host cell. The preparation method is simple and practical. The anti-HIV gene engineering medicament with the recombinant virus can effectively act on the HIV virus, and can further effectively prevent and treat the infection of the HIV virus.

The invention discloses a spiro heterocyclic ketone N-phenyl indole compound, its preparation method and application in controlling cardiovascular diseases and other medicine fields. The compound is formed by organically connecting spiro heterocycle, indole, phenyl ring and tetrazole, is an AT1 type acceptor retarding agent of angiotensin II, and can be used for preventing or treating hypertension, coronary heart disease, disease in blood vessels of heart, brain and kidney, hemicrania, pulmonary hypertension and other diseases.

The invention discloses a silver nanocluster imprinted polymer and an application thereof in targeted detection of tumor markers. Based on a designed PSA intelligent aptamer, specific binding abilityof the PSA intelligent aptamer is improved after optimization and modification. The PSA intelligent aptamer is used as a template to synthesize silver nanoclusters. Combined with specific recognitionadvantages of imprinted polymers, the silver nanocluster imprinted polymer is prepared; and the application of the silver nanocluster imprinted polymer to the targeted recognition of PSA in tumor tissues is explored. The present invention is expected to provide new research ideas for improving the targeted recognition of tumor markers and is of great significance for the clinic targeted diagnosisand treatment of cancers.

The invention provides a human angiotensin converting enzyme 2-based affinity polypeptide for the severe acute respiratory syndrome coronavirus 2, and relates to the technical field of biological materials. Key human angiotensin converting enzyme 2 amino acid residues of binding sites of human angiotensin converting enzyme 2 and the severe acute respiratory syndrome coronavirus 2 are extracted toreconstruct a peptide library, and the human angiotensin converting enzyme 2-based affinity polypeptide for the severe acute respiratory syndrome coronavirus 2 is obtained by screening; and then, a biological detection reagent is prepared from the affinity polypeptide, and thus, a new method is provided for detection of the severe acute respiratory syndrome coronavirus 2.

The invention discloses a polypeptide sequence specifically bind to polystyrene and a method for improving polypeptide and protein antigen for surface of a polystyrene material. By adopting a phage display random peptide library screening, the polypeptide PB-TUP which is subjected to affinity binding with polystyrene is obtained, an amino acid sequence is Val-His-Trp-Asp-Phe-Arg-Gln-Trp-Trp-Gln-Pro-Ser; and a coding nucleotide sequence is GTG-CAT-TGG-GAT-TTT-CGG-CAG-TGG-TGG-CAG-CCT-TCT. The method has the following advantages that 1) then affinity peptide PB-TUP has strong affinity binding capability on a polystyrene carrier; 2) the affinity peptide PB-TUP and polypeptide or protein antigen are fusion, so that the immobilized effect of antigen can be effectively improved; 3) the affinity peptide PB-TUP can guide the fusion antigen to immobilize on the surface of polystyrene by an unified and ordered mode, the space conformation of the antigen is kept, and the inactivation of antigen active sites due to shielding can be avoided; and 4) the method can be used for diagnosis detection technologies, such as enzyme linked immunosorbent assay, biology, cytological detection, and biosensors and micro-array chips which take the polystyrene as a fixed carrier, and improves detection sensitivity.

The invention provides a nano antibody targeting a methicillin-resistant staphylococcus LspA protein as well as a preparation method and application of the nano antibody. The provided nano antibody mainly recognizes a binding motif region combined with the methicillin-resistant staphylococcus LspA, and comprises a framework region FR and complementary determining regions CDR1, CDR2 and CDR3. One specific amino acid sequence of the nano antibody is SEQ ID NO: 1. The nano antibody disclosed by the invention can be efficiently and specifically combined with methicillin-resistant staphylococcus LspA protein, and the affinity can reach a nanomole level; and meanwhile, the nano antibody provided by the invention can obtain an excellent effect in methicillin-resistant staphylococcus detection or diseases caused by methicillin-resistant staphylococcus, and can be applied to the fields of biology and medicine.

The invention discloses a novel blue-light electrophoresis nucleic acid dye, a structural formula is shown in the specification, wherein R is C2-C4 alkyl groups. The novel blue-light electrophoresis nucleic acid dye has higher sensitivity and stability by comparing with common nucleic acid dyes, effectively improves the highly toxic characteristics of the traditional nucleic acid dyes, and can beused for agarose or polyacrylamide gel dyeing as the non-toxic nucleic acid dye.

The invention belongs to the technical field of monoclonal antibodies, and particularly discloses a new coronavirus RBD specific monoclonal antibody of which the heavy chain amino acid sequence is shown as SEQ ID NO: 1, the amino acid sequence of the light chain of which is shown as SEQ ID NO: 2. The invention also provides an application of the new coronavirus RBD specific monoclonal antibody. The invention has important scientific significance and application prospect in prevention of diseases caused by the novel coronavirus SARS-CoV-2, clinical treatment and research and development of diagnostic reagents.

The invention discloses a nucleic acid detection sensor based on S9.6 antibody bivalent capture, and belongs to the technical field of biological detection. The sensor comprises hairpin probes H0, H1 and H2, a single-chain probe I and an electrode or a chip which is self-assembled with an S9.6 antibody, the single-chain probe I is used for initiating H1 and H2 to generate a hybridization chain reaction so as to prepare a signal amplification material, in the presence of target nucleic acid, the hairpin probe H0 is recognized and opened and is hybridized with the prepared signal amplification material so as to form a compound, the compound contains two sections of DNA / RNA double strands, the DNA / RNA double strands are specifically recognized by an S9.6 antibody so as to be captured on a sensing interface, and the DNA / RNA double strands are captured by the S9.6 antibody. And determining the content of target nucleic acid by analyzing the signal change on the sensing interface. The method is suitable for any single-stranded nucleic acid detection, the detection process is simple, convenient and rapid, and high-sensitivity detection performance is obtained.

The invention discloses a novel anti-human β2 microglobulin single-domain antibody and its preparation method and application. The present invention utilizes phage display technology to perform multiple rounds of screening on the alpaca phage antibody library to enrich phages with β2 microglobulin specificity, prepare antibodies by culturing the phages, identify positive clones, and obtain their corresponding coding sequences by sequencing. Then expressed in E. coli to obtain soluble antibody fragments. The antibody of the present invention has the amino acid sequence shown in SEQ ID NO.1 or SEQ ID NO.10. The antibody provided by the invention has high binding ability to β2 microglobulin, can be used in the fields of blood purification and β2 microglobulin detection, and helps to promote and improve the diagnosis and treatment of diseases such as dialysis-related amyloidosis.

The invention provides a fluorescence-radioactivity combined in-vitro targeted screening method. The method comprises the following steps of: binding a drug to be detected to a solid phase carrier, and adding radionuclide labeled target molecules and fluorescent probe labeled same target molecules; after forming competitive bindings, synchronously detecting fluorescence and radioactive signals,obtaining two groups of data results which can be mutually verified and used for more accurately analyzing the binding capacity of the drug and the target molecules, thereby realizing targeted drug screening. The method provided by the invention can realize simultaneous detection of fluorescence and radioactive binding signal intensity of a plurality of to-be-detected drugs through a single test, andrapidly and efficiently screens out drugs with high specific binding capacity to target molecules. The method can effectively reduce the false positive probability, and has the characteristics of high flux, high accuracy, simple operation and the like. With the method adopted, antibody drugs specifically binding to target molecules can be rapidly screened out, pre-target antibodies can be developed for expanding indications of target radiopharmaceuticals in radioactive targeted therapy.

The invention relates to an anti-HIV genetic engineering divalent antibody and a preparation method thereof, and an anti-HIV genetic engineering medicine. The anti-HIV genetic engineering divalent antibody comprises a human antibody constant region and CD4 and CCR5 connected with the human antibody constant region. The preparation method of the anti-HIV genetic engineering antibody comprises the steps that: human antibody constant region gene, CD4 gene, and CCR5 gene are obtained; expression plasmids comprising the three genes are constructed; the expression plasmids are transfected into cell lines and are cultured; and the divalent antibody is obtained after separation and purification. The divalent antibody provided by the invention has both CD4 and CCR5 which can be specifically bound with CD4 and CCR5 loci on HIV virus, specific binding effect is substantially improved, and HIV-infected host cell dual inhibition can be realized. The preparation method provided by the invention is simple and feasible. The anti-HIV genetic engineering medicine with the divalent antibody can effectively act upon HIV virus, and assists in effectively preventing and treating HIV virus infections.

The invention belongs to the field of radiopharmaceutical chemistry and relates to a diaryl sulfide derivative, a preparation method thereof and application thereof as a serotonin transporter targeted imaging agent. The diaryl sulfide derivative has a structural formula shown in the description, exhibits high affinity with central SERT (serotonin transporter) and high selectivity for SERT relative to DAT (dopamine transporter) and NET (norepinephrine transporter). Therefore, the [18F]-diaryl sulfide derivative of the invention may act as an SERT / PET (positron emission tomography) imaging agent.

The invention discloses aheavy metal ion rapid detection method based on DNA hydrogel. Deoxyribonuclease based on metal ion dependence has high selectivity, specific binding capacity and good stability. The DNA enzyme is a functional nucleic acid and has a catalytic function of protease and a binding function of an antibody, and consists of a loop region for binding to a specific metal ion and hybridizing to its oligonucleotide substrate. After the deoxyribozyme is combined with the metal cofactor, the deoxyribozyme is activated, and the substrate can be divided into two chains. The fluorescent material combined on the chain is activated, the measured fluorescence signal is increased, the fluorescent material is used for sensitive lead quantification, and the detection limit is 1nM. Meanwhile, the detection method based on the DNA hydrogel also shows high selectivity to different metal ions, which is very important for analysis of complex samples.

The invention relates to a tenascin C nucleic acid aptamer GBI-10 modified with isonucleosides or isonucleosides combined with 2'-deoxyinosine, and a preparation method and applications thereof, belonging to the field of biomedicine. In the present invention, isonucleosides or isonucleosides combined with 2'-deoxyinosine are used to replace nucleotides in different positions of tenascin C nucleic acid aptamers GBI-10, so as to change the local spatial conformation of the nucleic acid aptamers, and optimize the Its spatial structure is obtained, thereby obtaining an isonucleoside or isonucleoside combined with 2'-deoxyinosine modified tenascin C nucleic acid aptamer GBI-10. Experiments show that the tenascin C nucleic acid aptamer GBI-10 modified by this method has stronger affinity with the target protein, more specific target recognition, and higher biological activity. Therefore, it is hoped that the isonucleosides or isonucleosides combined with 2'-deoxyinosine-modified tenascin C nucleic acid aptamer GBI-10 can be prepared into anti-tumor drugs with high efficiency, high selectivity, and low toxic and side effects. It is used in tumor early detection reagents.

The invention discloses a preparation method for a magnolol molecularly imprinted polymer film. The preparation method includes the following concrete steps: both imprinted molecule magnolol and solid-phase reagent are put into a ball mill and ball-milled, so that imprinted molecule inclusion compound is obtained, and the inclusion compound, functional monomer, cross-linking agent and initiator are put into porogen, ultrasonically degasified, then added with bond and ultrasonically stirred, so that mixture is obtained; filter paper is immersed in the mixture, taken out, clamped between two glass sheets, put into an oven and heated to be polymerized, so that polymer is obtained; imprinted molecules are removed from the obtained polymer, and after washing and drying, the magnolol molecularly imprinted polymer film is obtained. The preparation method adopts the mechanochemical technology to include the imprinted molecules, so that the ability of the imprinted molecules in specific binding with the functional monomer is enhanced, as a result, the recognition selectivity of the finally prepared molecularly imprinted polymer film is greatly enhanced, and the magnolol separation effect is good.