557results about "Glucagons" patented technology

The invention relates to the technical field of biology, in particular to a recombinant fusion protein, polynucleotide for coding the recombinant fusion protein, a recombinant expression plasmid containing the polynucleotide, an engineered recombinant host cell and a method for preparing target polypeptide by using the recombinant fusion protein. The recombinant fusion protein comprises tag polypeptide-target polypeptide-(linker 1-linker x-linker 2-target polypeptide) n from N terminal to C terminal, x is the number of linkers, x is 0 or 1, n is a positive integer not less than 1, the tag polypeptide is SEQ ID NO.1 or SEQ ID NO.2, the linker 1 contains a Kex2 protease enzyme cutting site and a carboxypeptidase B enzyme cutting site, and the linker 1 contains a Kex2 protease enzyme cutting site and a carboxypeptidase B enzyme cutting site. And the connecting peptide 2 contains a WELQ protease enzyme cutting site. The recombinant fusion protein disclosed by the invention is expressed in an inclusion body form, the synthesis process is simplified, the target polypeptide can be prepared with high yield and high purity by using the recombinant fusion protein disclosed by the invention, and the production cost can be reduced from multiple dimensions.

Fusion molecules comprising an obesity-related peptide moiety, fused to a myostatin pathway inhibitor moiety are disclosed. Also disclosed are nucleic acids and expression vectors encoding, compositions comprising, and methods of using, the fusion molecules.

Provided are β-eliminative linkers suitable for the conjugation of small molecule, peptide, and protein and compounds comprising the linkers.

Disclosed are GLP-1 agonists, and their use in the treatment of diseases such as diabetes, obesity, Alzheimer's disease, liver disease and cardiovascular diseases.

The invention relates to the technical field of medicines, in particular to a preparation method of semeglutide, which comprises the following steps: by optimizing a coupling sequence, firstly connecting a main peptide chain compound 1 with a side chain compound 5 without carboxyl protection, and then performing subsequent coupling with a dipeptide structure compound 6 with high steric hindrance, thereby obtaining the semeglutide. The problem of excessive modification caused by coexistence of a plurality of active sites in a traditional route is effectively avoided, especially for coupling difficulty brought by the structure of a compound 6, the types of a condensation reagent and a side-chain compound 5 are optimized, dipeptide carboxyl of the compound 5 is remarkably activated, amido bonds can be efficiently formed by the compound 5 and a compound 2 under the mild condition, and the compound 6 can be efficiently synthesized. In the path of synthesizing the compound 3 from the compound 1, one-pot operation is realized, and the reaction liquid in each step can be used for the next step without refining, so that the reaction time and the consumption of raw materials are reduced, and the connection efficiency and selectivity of key steps are greatly improved.

The invention relates to the field of biological medicine preparation, and particularly provides liraglutide precursor peptide tandem recombinant fusion protein, polynucleotide, recombinant expression plasmid, engineered host cell and a method for preparing target polypeptide. The recombinant fusion protein is fusion peptide-target polypeptide-(linker peptide-target polypeptide) n from the N terminal to the C terminal, n is a positive integer from 4 to 6, the fusion peptide is SEQ ID NO.1, the target polypeptide is liraglutide precursor peptide, the linker peptide comprises a spacer peptide and a protease restriction enzyme cutting site, the spacer peptide is SEQ ID NO.2, the isoelectric point of the recombinant fusion protein is 4.6-4.7, and the average hydrophilic value is-0.780--0.765. The proportion of the target polypeptide in the recombinant fusion protein is high, use of solvents under extreme conditions is avoided in the production process, the enzyme digestion efficiency is high, and the product purity and yield are high.

Provided are a method for constructing a soluble expression plasmid mutant library, and the use thereof. The method for constructing the soluble expression plasmid mutant library comprises: introducing mutations into a ribosome binding site on a soluble expression plasmid, a sequence composition and length of a region between the ribosome binding site and an initiation codon of a fusion protein to be expressed, and a translation initiation region, so as to obtain a mutant library. By means of the method, plasmid mutants with increased expression levels are obtained, thereby increasing the expression level of a target fusion protein and the final yield of a target polypeptide. The present invention solves the problem of low soluble expression levels of certain polypeptides in Escherichia coli.

The invention relates to the field of biological medicine preparation, and particularly provides canagliflozin precursor peptide tandem recombinant fusion protein, polynucleotide, recombinant expression plasmid, engineered host cell and a method for preparing target polypeptide. The recombinant fusion protein is a fusion peptide-target polypeptide-(linker peptide-target polypeptide) n from an N terminal to a C terminal, n is a positive integer of 4-6, the fusion peptide is SEQ ID NO.1 or SEQ ID NO.2, the target polypeptide is a canagliptin precursor peptide, the linker peptide comprises a spacer peptide and a protease restriction enzyme cutting site, the spacer peptide is SEQ ID NO.3, the isoelectric point of the recombinant fusion protein is 5.5-6.5, and the average hydrophilic value is-0.85--0.96. The invention creatively provides a method for preparing the canagliflozin precursor peptide by using a gene recombination technology, the proportion of the target polypeptide in the recombinant fusion protein is high, the use of a solvent under extreme conditions is avoided in the production process, the enzyme digestion efficiency is high, and the product purity and yield are high.

The present invention relates to formulations of glucagon analogues or pharmaceutically acceptable salts and / or derivatives thereof; and their medical use, e.g. in the treatment of hypoglycemia. In particular, the present invention relates to stable aqueous liquid formulations of glucagon analogues comprising a combination of excipients that make them suitable for long-term storage as liquids and capable of being used in single dose (SD) or multiple dose (MD) formulations.

The present invention relates to compounds comprising a GLP-1 receptor agonist and an amylin receptor agonist. The invention also relates to pharmaceutical formulations suitable for, but not limited to, oral administration, comprising such compounds. The compounds and pharmaceutical formulations comprising the same are useful in the medical treatment of subjects suffering from overweight, obesity and associated co-diseases.

Provided are novel compounds for GIPR, GLP-1R and GCGR. Specifically, provided are GLP-1R / GIPR / GCGR triagonists peptides, and conjugates comprising an Fc fragment and GLP-1R / GIPR / GCGR triagonists peptides. Pharmaceutical compositions comprising these compounds,as well as uses thereof in treating metabolic conditions and disorders, such as diabetes mellitus, type 2 diabetes, obesity, metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated steatohepatitis (MASH), and non-alcoholic steatohepatitis (NASH) are also provided.

Provided is a fusion protein, the fusion protein containing a GLP-1 polypeptide and an immunoglobulin Fc domain, wherein the GLP-1 polypeptide is covalently linked to the immunoglobulin Fc domain, the GLP-1 polypeptide is selected from human GLP-1(9-37) and human GLP-1(9-36) amides, and the GLP-1 polypeptide contains G22E and / or R36G substitutions relative to a natural human GLP-1 polypeptide. The human GLP-1(9-37) and human GLP-1(9-36) amides are products respectively resulting from losing two amino acids at the N-terminus of natural human GLP-1(7-37) and human GLP-1(7-36, by means of DPP4 enzyme degradation, and were previously considered as biologically inactive fragments. Provided are a polynucleotide encoding the fusion protein, a vector and cell containing the polynucleotide, and the use thereof, for example, in the preparation of drugs for treating metabolic diseases related to lipid metabolism disorders, complications of metabolic diseases, neurodegenerative diseases and other related diseases.

The present application provides O-tert-butyl-L-seryl-O-tert-butyl-L-seryl-glycine and a preparation method thereof. In the preparation process, N-benzyloxycarbonyl-O-tert-butyl-L-serine and O-tert-butyl-L-serine methyl ester are subjected to a condensation reaction to obtain an intermediate compound represented by formula (I), the compound represented by formula (I) and an alkaline compound are subjected to a saponification reaction to obtain an intermediate compound represented by formula (II), then the intermediate compound represented by formula (II) and glycine benzyl ester p-toluenesulfonate are subjected to a condensation reaction to obtain an intermediate compound represented by formula (III), and finally, the intermediate compound represented by formula (III) and hydrogen are subjected to a hydrogenation reaction to obtain the final product. The preparation method provided by the present application simplifies the process, features simple operation and mild reaction conditions, and reduces the difficulty of industrial production, and it does not involve precious raw materials and is conducive to controlling production costs, and the final product has a high purity and a high yield.

A composition that can activate both a class B and class C G-protein-coupled receptor (GPCR) simultaneously is described herein. This composition can be used in a variety of methods, and is exemplified by a HYBD-HEXA peptide, which is found in SEQ ID NO: 1.

The present invention relates to a use of a novel triple activator, having activity on all of GLP-1, GIP, and glucagon receptors, for preventing or treating lipid metabolic diseases.

The invention provides an engineered mesenchymal stem cell secreting GLP-1 / GIP dual agonist-Fc fusion protein and application of the engineered mesenchymal stem cell, and belongs to the technical field of biological medicine. The invention provides a GLP-1 / GIP dual agonist-Fc fusion protein. The fusion protein is formed by sequentially connecting four structural functional domains, namely a signal peptide, a human GIP (1-42) active fragment, a human GLP-1 (7-37) A8G mutant and an Fc fragment of human IgG4 through connecting peptides from an N end to a C end. And an engineering MSC cell strain (GE-MSC) which is derived from the iPSC and is used for expressing the GLP-1 / GIP dual agonist functional protein is constructed by adopting a gene editing technology. The invention creates an intelligent living body medicine factory which can be implanted at one time, autonomously target and stably secrete multifunctional therapeutic molecules for a long time, and has a tissue repair capability, so as to overcome multiple limitations of an existing protein medicine on compliance, medicine effect, cost and disease modification capability.

The present invention relates to a pharmaceutical composition for preventing or treating obesity, the composition comprising a glucagon-like peptide (GLP) analogue as an active ingredient. The GLP analogue of the present invention is an analog of GLP-1 and GLP-2 and has an extended duration of in vivo activity due to having an increased half-life, and thus was found to have an excellent effect in preventing or treating metabolic diseases. Specifically, the peptide of the present invention reduces the body weight and fat of an individual, reduces the levels of blood fat factors such as blood glucose, total blood cholesterol, high-density lipoproteins, low-density lipoproteins, and triglycerides, and reduces hepatic ASL and AST levels, liver weight, hepatic steatosis levels, and hepatic triglycerides levels, and thus can be effectively used as an excellent agent for preventing or treating metabolic diseases.

To provide potent GLP-1 agonists with reduced adverse effect and improved duration of action.SOLUTION: Provided is a novel Glucagon like Peptide- 1 (GLP-1) analogs having an amino acid sequence with Leu or Ile at the C-terminal, the GLP-1 analogs having specific sequences and modifications, requiring no frequent subcutaneous administration, also being suitable for oral administration, having a stable and long duration of action, and having a potent action of GLP-1 agonist.SELECTED DRAWING: None

The present disclosure relates to a method of capping, reducing, and oxidizing cys-mAbs in order to provide homogenous material for subsequent conjugation reactions. The present method demonstrates robust ways to manufacture conjugates of cysteine-engineered antibodies that offer high yield and consistent product quality.

The present disclosure provides peptides for reducing weight and / or preventing weight gain comprising a GLP-1R agonist. As described herein, the GLP-1R agonist can be administered orally to a subject.

Methods of improving nutrition in subjects, including individuals who have undergone gastrointestinal surgery, by avexitide therapy are disclosed. Avexitide may be administered subcutaneously or intravenously as a part of a liquid pharmaceutical formulation. Avexitide therapy may improve weight and / or nutritional intake / status in subjects.

Provided herein are peptides and peptide conjugates comprising a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. The peptides may be used for blood glucose management and treating conditions such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH).

The present disclosure provides methods for treating an inflammatory disease or disorder, wherein the inflammatory disease or disorder is a metabolic disease or disorder, comprising administration of a GLP-1 receptor agonist (e.g., semaglutide, exendin-4), and an IL-2 protein (e.g., aldesleukin) to a subject. Also presented herein are compositions for use with the methods disclosed herein and kits for administering a GLP-1 receptor agonist (e.g., semaglutide, exendin- 4), and an IL-2 protein (e.g., aldesleukin).

Disclosed are the dosages and dosing regimens of incretin analogs, including once-weekly dosing of long-acting incretin analogs suitable for once-weekly dosing, such as glucagon-like peptide-1 (GLP-1) and glucagon (Gcg) coagonists, and determining and administering such dosages.

The present invention relates to a biologically active material conjugate in which a biological active material is conjugated with a biotin moiety, a fatty acid moiety, or a combination thereof and, more specifically, to a biologically active material conjugate having a biotin moiety and a fatty acid moiety coupled thereto. With a biotin moiety and a fatty acid moiety coupled thereto, the biologically active material according to the present invention exhibits an excellent in-vivo oral absorption rate and has an excellent pharmacokinetic effect.

Disclosed are a synthesis system for a multi-copy peptide without redundant sequences, and a use. The synthesis system comprises a synthetic expression vector, wherein the synthetic expression vector comprises a tag-(linker-target polypeptide)n, n=1-10, n represents the number of copies, and the tag has an amino acid sequence selected from KPYDGP, KSKGEE, MTMITDSLAVVLQ, GFILGFIL or HHHHHH. The fusion tag enhances the expression of multi-copy polypeptides and results in a higher theoretical yield of the target polypeptide.

This specification provides an improved method for producing Fc-containing proteins. The method generally comprises culturing mammalian cells that produce Fc-containing proteins at a first pH setting for a first period of time, and then culturing the cells at a second pH setting higher than the first pH setting for a second period of time.