40results about "Parathyroid hormones" patented technology

The invention relates to the field of biological medicine, and discloses a pTH long-acting polypeptide compound as well as preparation and application thereof. According to the polypeptide, at least one amino acid residue of the 13th, 26th and 27th amino acid residues of a pTH (1-34) parent peptide sequence is connected with octadecanedioic acid or eicosanoic acid and a derivative modification group of octadecanedioic acid or eicosanoic acid, and the polypeptide is covalently combined with a polypeptide skeleton through an AEA-AEA-gamma-Glu connecting unit. The binding capacity of the polypeptide and serum albumin is remarkably enhanced by utilizing a fatty acid side chain modification means, and meanwhile, the half-life period is prolonged. The pTH long-acting polypeptide compound disclosed by the invention has remarkable osteogenic activity promoting effect, can promote proliferation of MC3T3-E1 cells and generate osteogenic markers and calcium nodules under osteogenic induction conditions, and the binding capacity of the pTH long-acting polypeptide compound and serum albumin is improved by 2-6 times. The invention further provides a solid-phase synthesis method of the polypeptide compound and a pharmaceutical composition containing the polypeptide compound, the polypeptide compound can be used for treating osteoporosis and parathyroid hypofunction, and the compliance problem that an existing medicine needs to be injected every day is effectively solved.

The invention discloses a method for synthesizing dipeptide Fmoc-Leu-Aib-OH, and belongs to the field of polypeptide synthesis, the specific preparation method comprises the following steps: under the action of organic alkali and an activating reagent, Fmoc-Leu-OH and H-Aib-OH react to obtain the dipeptide Fmoc-Leu-Aib-OH; the activating reagent comprises at least one of N, N, N ', N'-tetramethyl chloroformamidine hexafluorophosphate, 2-(7-azabenzotriazole)-N, N, N ', N'-tetramethyl urea hexafluorophosphate and benzotriazole-1-yl-oxytripyrrolidinyl phosphorus hexafluorophosphate, and the organic base comprises at least one of N-methylimidazole, N, N-diisopropylethylamine and pyridine. The dipeptide Fmoc-Leu-Aib-OH prepared by the preparation method disclosed by the invention is high in yield, high in purity and high in raw material conversion rate.

The invention relates to the technical field of biology, in particular to a nucleic acid molecule, a carrier containing the nucleic acid molecule, a host cell, a pharmaceutical composition and application of the nucleic acid molecule and the carrier. The nucleic acid molecule provided by the invention is particularly suitable for application scenes of gene therapy and treatment of various diseases.

The present invention relates to variants of TEV protease that have—compared to the wildtype enzyme—increased stability and catalytic activity as well as altered substrate specificity. The invention further relates to compositions comprising these variants as well as uses thereof and methods in which these variants are employed.

A linker for linking a therapeutic agent to another moiety, such as the Fc region of an antibody. A linker having two or more maleimide functional groups capable of undergoing a nucleophilic conjugate addition reaction. A method for increasing the duration of action of a therapeutic agent by conjugating it to a novel linker and the Fc region of an antibody. An antibody-drug conjugate having an increased duration of action over the drug alone.

Fusion compounds and methods of using same are provided which bind and neutralize human receptor activator of nuclear factor kappa-B ligand and are agonistic to parathyroid hormone receptor 1 signaling, said compounds are useful as agents for bone healing or treating conditions associated with bone mass loss or degeneration including treating osteoporosis.

The invention relates to the field of biological medicine, relates to a bifunctional fusion protein and application thereof, and more specifically relates to a polypeptide construct containing an antigen binding domain capable of specifically binding to RANKL and PTH peptide, and related application of the polypeptide construct in disease treatment.

Provided is a PTH1 ligand-bound nucleic acid complex that is delivered to a desired organ and that is for regulating the expression or editing of a target gene, a transcript thereof or a translation product thereof.　This PTH1 ligand-bound nucleic acid complex, which has a structure wherein a PTH1 ligand is bound to a nucleic acid, said nucleic acid containing an antisense strand containing an oligonucleotide that has a nucleic acid base sequence complementary to a target transcript and that comprises 12-30 nucleotides, is delivered to an organ and regulates the expression or editing of a target gene, a transcript thereof or a translation product thereof, which makes the complex useful in treating a disease caused by the gene. Further, the ligand-bound nucleic acid complex can be delivered to organs, tissues and cells in which PTH1 receptors are expressed, for example tissues such as that of the kidney, bones, and subcutaneous fat, and cells such as vascular endothelial cells, which makes the complex useful in treating diseases in these organs.

The present invention relates to the field of biomedicine. More specifically, the present invention relates to a polypeptide construct comprising an antigen binding domain capable of specifically binding to RANKL, and a PTH peptide, and a related use thereof for disease treatment.

The present invention relates to peptide modifier compounds of Formula (1), or a salt thereof, wherein: a is an integer from 1 to 10, more preferably from 1 to 3; b is an integer from 0 to 7; Z is a terminal group and Y is a bivalent group. Further aspects of the invention relate to intermediates in the preparation of compounds of Formula (1), and the use of compounds of Formula (1) in the synthesis of peptide derivatives.

Provided herein are methods of analyzing samples from batches of abaloparatide for abaloparatide and abaloparatide-related peptide impurities.

The application relates to the technical field of medicines, and discloses arginine glycosylation modified teriparatide and application thereof. First, a glycosylation donor is synthesized through a chemical synthesis method, then, according to a template PTH: SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF-NH2 amino acid sequence, arginines at positions 20 and 25 are replaced by ornithine with a Dde protecting group, the arginine glycosylation modified teriparatide is obtained by using the glycosylation donor to modify the same through a solid-phase synthesis method. The method is simple and easy to implement, has high purity and high yield. Further experiments prove that the arginine glycosylation modified teriparatide can significantly promote osteoblast differentiation, has high serum stability, and has potential application value in the treatment of diseases such as osteoporosis.

Disclosed are peptide-fatty acid conjugates, pharmaceutical compositions containing them, and methods of their medical use in the treatment of, e.g., a disease or condition associated with the PTHR1 signaling overactivity (e.g., hypercalcemia, hypophosphatemia, hyperparathyroidism, or Jansen's metaphyseal chondrodysplasia) or deficiency (e.g., hypoparathyroidism, hyperphosphatemia, osteoporosis, fracture repair, osteomalacia, arthritis, thrombocytopenia, or chronic kidney disease).

This invention relates to the field of biomedicine, disclosing a long-acting pTH polypeptide compound and its preparation and application. The polypeptide has an octadecanoic acid or eicosanoic acid and its derivatives modified by at least one amino acid residue at the 13th, 26th, and 27th amino acid residues of the pTH (1-34) parent peptide sequence, and is covalently bound to the polypeptide backbone via an AEEA-AEEA-γ-Glu linker. This invention significantly enhances the binding ability of the polypeptide to serum albumin and prolongs its half-life by utilizing fatty acid side chain modification. The long-acting pTH polypeptide compound of this invention exhibits significant osteogenic activity, promoting the proliferation of MC3T3-E1 cells and generating osteogenic markers and calcium nodules under osteogenic induction conditions, with a 2-6 fold increase in binding ability to serum albumin. This invention also provides a solid-phase synthesis method for this polypeptide compound and a pharmaceutical composition containing it, which can be used to treat osteoporosis and hypoparathyroidism, effectively solving the compliance problem of existing drugs requiring daily injections.

The invention belongs to the technical field of biology, and particularly relates to a human parathyroid hormone 1-34 peptide analogue and a preparation method and application of the human parathyroid hormone 1-34 peptide analogue, and the human parathyroid hormone 1-34 peptide analogue is formed by peptide fragments shown in SEQ ID No.1-SEQ ID No.8 or homologous peptide fragments of the peptide fragments. The human parathyroid hormone 1-34 peptide analogue has osteoporosis treatment activity, is used for relieving parathyroid hypofunction and related symptoms after parathyroid gland resection or extirpation, and also has an erection promoting function, and the preparation method is economical and environment-friendly, is suitable for industrial development and has a wide prospect.

This disclosure concerns production of product peptides with a target amino acid sequence by proteolysis of a recombinant polypeptide comprising specific protease recognition sites or chemical cleavage sequences. In some embodiments, the product peptide is released from repeating peptide units in the recombinant polypeptide by removal of intervening amino acid sequences by proteolysis by proteases that recognize sites within the intervening amino acid sequences and a carboxypeptidase, aminopeptidase, and / or further protease.

The application discloses a bone inductive active polypeptide capable of being assembled into nanofiber hydrogel and application thereof. The bone inductive active polypeptide comprises an assembly domain at a C terminal, a bone inductive active domain at an N terminal and a flexible connection separation domain between the two. The assembly domain is (RADA) 4‑9 The bone inductive active domain is parathyroid hormone (PTH) or parathyroid hormone related peptide (PTHrP). The bone inductive active polypeptide can be spontaneously assembled into a peptide nanofiber, and can be co-assembled into a peptide nanofiber hydrogel by mixing with RADA16 peptide. The hydrogel assembled from the bone inductive active polypeptide and the high-molecular composite nanobiomaterial constructed by the hydrogel can effectively avoid polypeptide burst release, avoid polypeptide degradation by local proteases, replace long-term systemic systemic administration of PTH and PTHrP, improve patient compliance and reduce patient pain. The application provides a new strategy for in-situ bone repair of PTH and PTHrP.

This invention discloses a method for targeted screening of teriparatide-producing bacteria using antibiotics. Through two rounds of screening with different concentrations of antibiotics, E. coli strains capable of high teriparatide expression are obtained, and the plasmid stability is effectively maintained during strain passage without the addition of antibiotics. This targeted screening method not only effectively improves the screening efficiency of high teriparatide-producing bacteria but also overcomes the technical difficulty of adding antibiotics during the production of biopharmaceuticals.

Disclosed are peptide-fatty acid conjugates, pharmaceutical compositions containing them, and methods of their medical use in the treatment of, e.g., a disease or condition associated with the PTHR1 signaling overactivity (e.g., hypercalcemia, hypophosphatemia, hyperparathyroidism, or Jansen's metaphyseal chondrodysplasia) or deficiency (e.g., hypoparathyroidism, hyperphosphatemia, osteoporosis, fracture repair, osteomalacia, arthritis, thrombocytopenia, or chronic kidney disease).

A recombinant PTH fusion protein, a construction method therefor, and an application thereof. The recombinant PTH fusion protein comprises: A1) at least one signaling domain molecule capable of activating a PTHR1 intracellular pathway; A2) a molecule having one or more ECDs capable of binding to the PTHR1; A3) a human serum albumin nanobody, wherein an amino acid sequence of the human serum albumin nanobody is as shown in SEQ ID NO: 7. The recombinant PTH fusion protein is capable of effectively improving the duration and magnitude of pharmacodynamic action, increasing blood calcium levels within 24-48 hours, and returning to normal levels within 48-72 hours. Said protein has excellent temperature stability and freeze-thaw stability, and can be used for treating and / or preventing hypoparathyroidism. In addition, the preparation method for the recombinant PTH fusion protein is simple and can be used for industrial production.

The present invention relates to the field of biomedicine, and more particularly, the present invention relates to a complex of PTH protein or an active fragment thereof and an antibody or a fragment thereof that specifically binds to PTH, and a related use thereof in disease treatment.

The invention relates to the technical field of polypeptide drugs, and provides a synthesis method of abparatide, which comprises the following steps: by taking Rink Amide AM resin, Rink MBHA resin or Rink Amide resin as a solid-phase carrier, sequentially coupling single amino acid and 19-21 tripeptide fragments or 19-22 tetrapeptide fragments from N terminal to C terminal through a solid-phase synthesis method according to a primary sequence of abparatide, so as to obtain abparatide peptide resin; the abparatide peptide resin is cracked to obtain abparatide, and a coupling agent / alkali adopted for coupling is selected from at least one of Oxyma / DIC, COMU / DIEA, COMU / TMP, PyOxim / DIEA and TPTU / DIEA. The abparatide crude peptide synthesized by the method disclosed by the invention is high in yield and high in purity, and the synthesis method disclosed by the invention shortens the production time, reduces the production cost and is beneficial to commercial production.

Disclosed herein are compounds and methods for treating osteogenesis imperfecta in individuals.In some embodiments, the compounds comprise bone anabolic agents, linkers and bone targeting ligands.In some embodiments, the methods comprise reducing the occurrence or likelihood of bone fracture, increasing bone density or bone strength, and providing compounds to the low density bone sites and weakened bone sites in individuals with osteogenesis imperfecta.

The invention belongs to the technical field of polypeptide liquid-phase synthesis carriers, and discloses a soluble liquid-phase carrier for polypeptide liquid-phase synthesis and application of the soluble liquid-phase carrier. The structural formula of the soluble liquid phase carrier for polypeptide liquid phase synthesis is shown in the specification, in the formula, 1-3 groups R are selected from H, methoxyl, halogen, alkyl, aldehyde group and nitryl; the number of the group Linker-Tag is 1 to 3; when the soluble liquid-phase carrier is applied to polypeptide liquid-phase synthesis, the soluble liquid-phase carrier not only shows excellent performance in the aspects of improving the operation efficiency, conveniently monitoring the reaction process and the like, but also has the advantages of economical efficiency and sustainable use, can remarkably improve the efficiency and controllability of the polypeptide liquid-phase synthesis process, and has extremely high practicability.

The invention discloses a long-acting parathyroid hormone receptor stimulant fusion protein and application thereof. The fusion protein can inhibit the activity of RANKL and promote PTHR-mediated bone anabolism, and comprises a first arm and a second arm, the first arm comprises a functional region targeting RANKL and an Fc region, and the second arm comprises a functional region capable of activating PTHR and an Fc region. The long-acting parathyroid hormone receptor stimulant fusion protein has the advantages of better drug effect, more lasting effect, better safety, higher structural stability, higher expression quantity and the like, and the comprehensive performance of the long-acting parathyroid hormone receptor stimulant fusion protein is superior to that of the existing or potential treatment means such as teriparatide, PEG-PTH, anti-RANKL monoclonal antibody, romomonoclonal antibody or a control sample synPTH-alpha RANKL-1.

The present invention relates to a PTH compound for use in the treatment of chronic hypoparathyroidism, wherein the treatment comprises administering a weekly dose of the PTH compound to a patient having chronic hypoparathyroidism, and wherein prior to initiation of treatment, the patient is clinically determined to no longer be dependent on active vitamin D and calcium supplements to maintain serum levels within the normal range, and related aspects.

Provided herein are methods of analyzing samples from batches of abaloparatide for abaloparatide and abaloparatide-related peptide impurities.

A recombinant PTH fusion protein, a construction method therefor, and an application thereof. The recombinant PTH fusion protein comprises: A1) at least one signaling domain molecule capable of activating a PTHR1 intracellular pathway; A2) a molecule having one or more ECDs capable of binding to the PTHR1; A3) a human serum albumin nanobody, wherein an amino acid sequence of the human serum albumin nanobody is as shown in SEQ ID NO: 7. The recombinant PTH fusion protein is capable of effectively improving the duration and magnitude of pharmacodynamic action, increasing blood calcium levels within 24-48 hours, and returning to normal levels within 48-72 hours. Said protein has excellent temperature stability and freeze-thaw stability, and can be used for treating and / or preventing hypoparathyroidism. In addition, the preparation method for the recombinant PTH fusion protein is simple and can be used for industrial production.

A PTH(1-34) mimetic peptide and a pharmaceutical composition for preventing or treating osteoporosis or promoting bone growth are provided. The mimetic peptide contains peptide fragment repeats at 29th-34th positions. Structure of the mimetic peptide is PTH(1-F34Y)(29-F34Y), and the amino acid sequence of the mimetic peptide is SEQ ID NO: 3. The pharmaceutical composition includes an active ingredient and a pharmaceutically acceptable carrier. The active ingredient of the pharmaceutical composition contains the PTH mimetic peptide.