22 results about "Anti proteases" patented technology

The invention provides a cyclic peptide as well as a preparation method and application thereof. The cyclic peptide has an amino acid sequence # imgabs0 # represented by formula (1) (wherein X is a Lys residue modified with a fatty acid molecule, and a line connecting Arg and Lys represents an amide bond. The cyclic peptide prepared by the invention has wide antifungal activity and antibacterial activity on drug-resistant bacteria; meanwhile, the biotoxicity and the protease degradation resistance are high, and the in-vivo antibacterial effect of the cyclopeptide can be prolonged. The cyclic peptide can be applied to preparation of anti-bacterial and anti-fungal infection drugs, and can be used as an excellent substitute drug or an auxiliary drug of existing antibiotics. The method for preparing the cyclic peptide is simple, raw materials are easy to obtain, and industrial production can be achieved.

The invention relates to an anti-hair loss and hair growth peptide with alternately arranged D / L amino acids as well as a preparation method and application of the anti-hair loss and hair growth peptide, and belongs to the technical field of biological medicines. The amino acid sequence of the polypeptide is shown as SEQ ID NO: 1, D-type and L-type amino acids are alternately arranged and designed, the protease degradation resistance is remarkably enhanced, the in-vitro half-life period is larger than or equal to 48 hours, and beta-catenin protein expression in hair follicle stem cells is activated. The preparation method comprises the following steps: taking Rink Amide resin as a carrier, sequentially coupling D / L type amino acid by adopting an Fmoc solid-phase synthesis method, cracking the resin by trifluoroacetic acid, and purifying by high performance liquid chromatography, so that the yield is more than or equal to 80%, the purity is more than or equal to 96%, and the molecular weight is confirmed to be 956.12 Da by mass spectrometry. The polypeptide can be applied to preparation of anti-hair loss and hair growth cosmetics, medicines and medical instruments, and effectively solves the problems of low stability and insufficient targeting of the polypeptide in the prior art. # imgabs0 #

The present invention relates to the technical field of genetic engineering. Particularly provided are an identification marker for early chronic obstructive pulmonary disease and the use thereof in a diagnostic kit. The identification marker for the early chronic obstructive pulmonary disease is screened, which is miRNA1255a in serum-derived exosomes; in addition, biological function analysis after sequencing proves that among a plurality of target genes of miRNA1255a, the tissue inhibitor of metalloprotease (TIMP-2) and CD36, which are genes related to the protease / antiprotease balance, are involved in the Ca ion signaling pathway, and moreover, the expression of CD36 and TIMP-2 proteins proves that said two proteins are negatively correlated with miRNA1255a. Moreover, it is found in detection results that the expression of TIMP-2 and the expression of CD36 are all downregulated when the expression of miRNA1255a is upregulated. The biomarker for the early chronic obstructive pulmonary disease is provided, which can easily screen potential patients with early onset of chronic obstructive pulmonary disease.

The invention discloses a cationic peptide compound for targeting cartilage as well as a preparation method and application of the cationic peptide compound. The cationic peptide compound has a structural general formula as shown in the specification: R-(Xa-Nlys-Yb) n, wherein R is H, a drug active molecule or a group containing a signal marker, and X and Y are independently selected from any one of glycine residues and imidic acid residues; nlys is a residue of N-(4-aminobutyl) glycine; a and b are independently selected from any integer between 0 and 3; n is any positive integer from 3 to 10. The compound can target a glycosaminoglycan chain in cartilage through electrostatic interaction, has an effect of resisting protease degradation, and is beneficial to prolonging the in-vivo circulation time. The compound supports systemic administration, can be used for marking whole body cartilage through intravenous injection, is used for monitoring cartilage development, aging and pathological changes in real time, and has wide application potential in the aspects of molecular imaging, drug delivery and biological materials for treating cartilage-related diseases.

The invention belongs to the field of biosensing and biological interface engineering, and particularly relates to a double-enhanced bionic glycopeptide electrochemical biosensor based on anti-pollution and anti-enzymolysis stability and a preparation method of the double-enhanced bionic glycopeptide electrochemical biosensor. The invention is inspired by glycoprotein in vascular endothelial cell glycocalyx, a novel glycopeptide material capable of enhancing biological pollution resistance and protease hydrolysis resistance stability is constructed by performing glycosylation modification at the C terminal of a polypeptide sequence, and the novel glycopeptide material is applied to a complex biological medium and has remarkable performance superior to that of non-glycosylated peptide.

The invention relates to the field of microbiology, in particular to lactobacillus plantarum A3 and application thereof. The lactobacillus plantarum is named as lactobacillus plantarum A3, the preservation number is CCTCC (China Center for Type Culture Collection) NO: M 2026320, and the preservation unit is China Center for Type Culture Collection. According to the invention, a safe lactobacillus plantarum A3 is successfully separated and obtained, and a novel bacteriocin Plantaricin A3 is identified from the safe lactobacillus plantarum A3; the bacteriocin Plantaricin A3 has excellent thermal stability, pH stability and protease hydrolysis resistance, is wide in antibacterial spectrum, particularly has a remarkable effect on aquatic pathogenic vibrio, and has a wide application prospect in the fields of food, feed and aquaculture.

The invention discloses a preparation method of high-stability superoxide dismutase (SOD), and belongs to the technical field of bioengineering and enzyme engineering. The method comprises the following steps: chemically modifying purified SOD (superoxide dismutase) under the conditions of low temperature and neutral pH (potential of hydrogen) by taking monomethoxy polyethylene glycol succinimido active ester as a modifier; carrying out ultrafiltration preliminary purification on the reaction liquid, then carrying out deep purification through ion exchange chromatography, and separating to obtain a high-purity modified product; and finally, sterilizing, filtering and freeze-drying to obtain the freeze-dried powder. According to the method, by optimizing a modification and purification process, the thermal stability and protease degradation resistance of SOD are remarkably improved, and meanwhile, most enzyme activity of SOD is effectively reserved. The prepared PEG-SOD product is high in purity and good in stability, and is suitable for preparing anti-inflammatory, anti-oxidation or anti-aging medicines and functional foods.

The present application relates to a kind of D / L amino acid alternate arrangement anti-hair loss hair growth peptide and its preparation method and application, belong to biological medicine technical field.The amino acid sequence of the polypeptide is as shown in SEQ ID NO:1, is designed by D type and L type amino acid alternate arrangement, significantly enhance the ability of anti-protease degradation, in vitro half-life is ≥48 hours, and activate β-catenin protein expression in hair follicle stem cell.Its preparation method includes: using Rink Amide resin as carrier, using Fmoc solid-phase synthesis method sequentially coupling D / L type amino acid, after cleaving resin by trifluoroacetic acid, by high performance liquid chromatography purification, yield is ≥80%, purity is ≥96%, mass spectrum confirms molecular weight is 956.12Da.The polypeptide can be applied to the preparation of anti-hair loss hair growth cosmetics, drugs and medical devices, effectively solve the problem of low polypeptide stability, insufficient targeting in prior art.

The invention discloses a compound preparation for regulating vaginal microecology as well as preparation and application thereof, and relates to the field of biological medicines. The composite preparation is composed of a fusion polypeptide and a monoclonal antibody according to the ratio of 1: 2 (w / w), the fusion polypeptide comprises a cell adhesion domain, an enzymolysis linking peptide and a quorum sensing inhibition domain, the amino acid sequence is shown as SEQ ID NO: 1, and the protease hydrolysis resistance is improved by more than 4 times after cyclization oxidation; the monoclonal antibody takes specific surface protein of lactobacillus inertus as a target spot, and can induce the strain to generate H2O2 phenotype conversion. An in-vitro experiment shows that the degradation rate of the composite preparation on a vaginal bacterial biofilm reaches 92.3 + / -2.4%, the ratio of lactobacillus acidophilus is remarkably increased to 63.8 + / -3.3%, and the pH is effectively adjusted to 4.3; animal experiments show that compared with commercially available metronidazole gel, the compound preparation can more remarkably promote proliferation of lactobacillus, inhibit escherichia coli and staphylococcus aureus and restore vaginal micro-ecological balance, and a new scheme is provided for treatment of vaginal micro-ecological imbalance related diseases.

The present invention relates to recombinant proteins having an amino acid sequence corresponding to or related to the thrombospondin type 1 repeat homology domain of a member of the CCN family proteins and the use thereof. Furthermore, the present invention relates to fusion proteins comprising an amino acid sequence corresponding to or related to the thrombospondin type 1 repeat homology domain of a member of the CCN family proteins combined with a fusion partner and optionally a linker region. Also, novel protease resistant Fc-fragments are disclosed herein.

The application discloses an enzyme mutant with improved thermal stability and a gene and application thereof, and relates to the technical fields of genetic engineering and enzyme engineering. The application provides a mannanase mutant Man74s, and an amino acid sequence of the mannanase mutant Man74s is shown as SEQ ID NO:2. The mannanase mutant Man74s has high thermal stability, and has high activity in an acidic and neutral range at normal temperature, and other characteristics such as resistance to protease degradation, the optimal pH value of the mannanase mutant Man74s is 6.0, the mannanase mutant Man74s has relatively high catalytic activity in the pH range of 5.0-7.0, the optimal temperature is 50 DEG C, the residual enzyme activity of the mannanase Man74s is still above 70% after being treated at 85 DEG C for 3 min, and the mannanase Man74s is suitable for a rumen animal environment such as a cow or a sheep.

The invention discloses an enzyme mutant with improved thermal stability and a gene and application thereof, and relates to the technical field of gene engineering and enzyme engineering. The invention provides a mannase mutant Man74s, wherein the amino acid sequence of the mannase mutant Man74s is as shown in SEQ ID NO: 2. The mannase mutant Man74s disclosed by the invention has high thermal stability and has the characteristics of high activity, protease degradation resistance and the like in acidic and neutral ranges at normal temperature, the optimal pH value of the mannase mutant Man74s is 6.0, and the mannase mutant Man74s has relatively high catalytic activity in a pH range of 5.0-7.0; the optimal temperature is 50 DEG C, the residual enzyme activity is still 70% or above after mannase Man74s is treated at 85 DEG C for 3 min, and the mannase Man74s is suitable for rumen animal environments such as cattle and sheep.

The invention belongs to the field of medicines, and particularly relates to a CD71-targeting ROS responsive micelle as well as a preparation method and application thereof. In order to improve the efficacy of an anti-tumor drug in treating AML patients and reduce toxic and side effects, the invention provides a nano drug delivery system, namely a CD71-targeted ROS responsive micelle, which comprises the following components: amphiphilic molecules with ROS response, DSPE-PEG-DT7 and an anti-tumor drug. The micelle provided by the invention adopts a small molecule polypeptide ligand, so that competition with endogenous Tf is avoided, the micelle has protease digestion resistance, and the targeting property in blood and the in-vivo stability are improved; an amphiphilic block containing ROS responsiveness is introduced as a micelle skeleton, so that specific drug release in AML cells is realized, the curative effect is enhanced, and the side effect is reduced; aiming at AML (acute myelogenous leukemia) cells with ROS (reactive oxygen species) rise caused by FLT3-ITD mutation, the micelle disclosed by the invention can be used for effectively releasing drugs and generating a stronger drug effect reaction.

The invention provides application of phosvitin in preparation of a medicine for treating inflammatory bowel diseases. The inflammatory bowel disease comprises ulcerative colitis, and the ulcerative colitis is colitis induced by DSS (Di-Sulfate Sodium Sulfate). The phosvitin is natural protein extracted from eggs and has no adverse reaction on human bodies, and discomfort caused by long-term anti-inflammatory drug treatment is avoided. The phosvitin provided by the invention has the property of high net negative charge, so that the phosvitin has an anti-proteolysis effect, can resist a stomach high-acid environment, reaches intestinal tracts and exerts a curative effect.

The invention discloses an anti-protease K monoclonal antibody and application thereof. A heavy chain variable region of the antibody comprises the following complementarity determining regions: VH-CDR1 as shown in SEQ NO.2, VH-CDR2 as shown in SEQ NO.4 and VH-CDR3 as shown in SEQ NO.6; the light chain variable region comprises the following complementarity determining regions: VL-CDR1 as shown in SEQ NO.9, VL-CDR2 as shown in SEQ NO.11 and VL-CDR3 as shown in SEQ NO.13, and the VH-CDR1-3 and the VL-CDR1-3 jointly form a protease K binding site. The anti-proteinase K monoclonal antibody can be applied to various nucleic acid detection technologies such as PCR, qPCR and reverse transcription PCR, the use process is simple, the anti-proteinase K monoclonal antibody is directly added to a reaction system, the activity of the proteinase K can be effectively inhibited without a pretreatment step, the active site of the proteinase K can be accurately targeted through the specific inhibition effect, the activity of the proteinase K can be specifically blocked, and meanwhile, the application range of the anti-proteinase K monoclonal antibody is widened. The activity of common nucleic acid polymerase (Taq, reverse transcriptase and the like) is not obviously influenced, complete neutralization can be realized at a low dosage, and excellent high efficiency is shown.

The invention belongs to the field of biological medicines, and relates to a pharmaceutical composition of a protease drug and an immunomodulator for treating phenylketonuria, which has the technical scheme that the protease drug and the immunomodulator for treating phenylketonuria are combined, so that the generation of an anti-protease drug antibody can be effectively reduced, and the curative effect is improved. The in-vivo action time of the protease medicine is prolonged. The invention has the beneficial effects that the combined drug can effectively reduce the immunogenicity of the protease drug, reduce the generation of in-vivo drug antibodies, prolong the action time of the drug, reduce the administration frequency of the protease drug, greatly improve the compliance of patients with phenylketonuria, and reduce the cost. Therefore, the combined medicine can be widely applied to treatment of phenylketonuria.

The present invention relates to the fields of genetic engineering and enzyme engineering. Provided are an enzyme mutant with improved thermostability, a gene thereof and the use thereof. Provided is a β-mannanase mutant. Compared with an amino acid sequence as shown in SEQ ID NO: 2, the β-mannanase mutant contains at least one of the following mutations: V86Y, A248P, and H317N. The β- mannanase mutant has an optimum pH of 6.0, has a relatively good enzymatic activity, pH stability and thermostability at pH 3.5-7.0, and has a relatively good protease resistance. The β-mannanase mutant has broad application prospects in food, feed, papermaking and textiles.

Protease nexin-1 (PN-1) is a member of the serine protease inhibitor (Serpin)-family, with thrombin as its main target. Current polyclonal and monoclonal antibodies against PN-1 frequently cross-react with Plasminogen activator inhibitor-1 (PAI-1), a structurally and functionally homologous Serpin. Herein the inventors develop inhibitory single-domain antibodies (VHHs) showing specific binding to both human (hPN-1) and murine (mPN-1) PN-1 and which de not cross-react with PAI-1. Importantly, all VHHs could block PN-1 activity in plasma as well as PN-1 released from activated platelets, one of the main sources of PN-1 during hemostasis. Thus, the present invention relates to anti-protease nexin-1 (PN-1) conformational single domain antibodies and uses thereof in particular in the therapeutic field for the treatment of haemorrhagic diseases.

A protease-resistant ADAMTS13 mutant protein or nucleic acid encoding the ADAMTS13 mutant protein is provided. The ADAMTS13 mutant protein comprises a mammalian ADAMTS13 protein in which one or more protease cleavage sites within the protein are replaced with amino acid sequence that is resistant to protease cleavage, and the mutant protein retains von Willebrand factor (VWF)-cleaving activity. The protease-resistant ADAMTS13 mutant is useful as a thrombolytic agent to treat common thrombotic disorders, including stroke, myocardial infarction, venous thromboembolism, and rare microvascular thrombotic disorders like thrombotic thrombocytopenia purpura (TTP).

The invention relates to the technical field of albendazole treatment, and particularly discloses a pharmaceutical composition for treating albendazole, 2-8 parts of nefenavir, 30-50 parts of polylactic acid-glycolic acid copolymer (PLGA), 5-15 parts of chitosan, 3-8 parts of sodium cholate and 1-3 parts of vitamin E succinate. The pharmaceutical composition is prepared from the following raw materials in parts by weight: 5-15 parts of albendazole, 2-8 parts of nefenavir, 30-50 parts of polylactic acid-glycolic acid copolymer (PLGA), 5-15 parts of chitosan, 3-8 parts of sodium cholate and 1-3 parts of vitamin E succinate. 20 to 35 parts of lactose and 0.5 to 2 parts of magnesium stearate. The albendazole can inhibit synthesis of polypide microtubulin, the nefenavir is an anti-HIV protease inhibitor and can assist the albendazole to penetrate through the cyst wall of echinococcal, penetrability is enhanced through drug combination, the problem that the albendazole is limited in curative effect and depends on host immunity is solved, the albendazole and sodium cholate form a eutectic crystal, and the albendazole-sodium cholate co-crystal is used for preparing the albendazole-sodium cholate co-crystal. The dissolution behavior is effectively improved; in addition, as an antioxidant, vitamin E succinate can reduce oxidative degradation of albendazole in an acid environment, and the vitamin E succinate and the PLGA-chitosan slow release system cooperate to guarantee the drug stability.

The invention belongs to the technical field of polypeptide related drugs, and discloses an isopeptide bond-containing antibacterial peptide analogue and application thereof, based on the structural characteristics of the conventional lysine-containing antibacterial peptide sequence VWRKWRRFWKR-NH2, the sequence contains two Lys residues which are easy to become restriction enzyme cutting sites of some specific proteases, so that the sequence is unstable in vivo and easy to hydrolyze. Based on the defect, an isopeptide bond is introduced into a sequence by changing a connection mode of two amino groups contained in a lysine residue at a specific site in the sequence, but the size, the sequence sequence, the charge and the molecular weight of the whole antibacterial peptide sequence are not changed, so that the method aims at improving the proteolysis resistance of the antibacterial peptide, and improving the proteolysis resistance of the antibacterial peptide. The toxicity and the hemolysis are reduced. The problem that the antibacterial peptide is easily subjected to enzymolysis is solved from the source, and the key bottleneck of oral medication is overcome, so that the problem of high cost in the production process of preparing an anti-enzymolysis antibacterial peptide preparation is relieved, and the clinical application of the antibacterial peptide is promoted.

The invention belongs to the technical field of antibacterial peptides, and particularly relates to an antibacterial peptide and application thereof. The antibacterial peptide provided by the invention has a remarkable inhibition effect on gram-positive bacteria such as staphylococcus aureus and enterococcus faecalis and gram-negative bacteria such as escherichia coli and acinetobacter baumannii, and the MIC value of the antibacterial peptide is 4-32 mu g / mL. Safety experiments show that under the concentration of 300 g / mL, the hemolysis rate of the antibacterial peptide is smaller than 5%; the concentration of AMP1-AMP3 is sequentially lower than 100 g / mL, 800 g / mL and 100 g / mL, the survival rate of human corneal epithelial cells is larger than 85%, toxic and side effects are small, and biocompatibility is good. Stability experiments show that the antibacterial peptide has good pH stability, thermal stability, ultraviolet irradiation stability and protease hydrolysis resistance. The antibacterial peptide provided by the invention is short in amino acid sequence, relatively low in synthesis cost, large in yield, relatively good in repeatability, high in stability and low in toxicity, and shows broad-spectrum antibacterial activity.