1313results about "Glucagons" patented technology

The invention provides a polypeptide or a derivative and a pharmaceutically acceptable salt thereof. The amino acid sequence of the polypeptide is as shown in SEQ ID NO: 1. The polypeptide or the derivative and the pharmaceutically acceptable salt thereof disclosed by the invention can be combined with GLP-1R and GCGR, and is used for effectively activating the GLP-1R and the GCGR. Therefore, the polypeptide or the derivative and the pharmaceutically acceptable salt thereof can be used for detecting GLP-1R and / or GCGR, and can also be used for treating or preventing GLP-1R and / or GCGR related diseases (such as metabolic disorder related diseases, such as obesity, diabetes, fatty liver diseases, non-alcoholic fatty liver diseases and the like).

The invention provides an anti-human serum albumin nano antibody and application thereof, and belongs to the technical field of antibodies. The invention provides an anti-human serum albumin nano antibody HSA-32 with relatively high affinity, and the anti-human serum albumin nano antibody HSA-32 is subjected to humanized transformation, so that three obtained humanized anti-human serum albumin nano antibodies can be used for reducing the immunogenicity of the HSA-32 and improving the immunogenicity of the HSA-32; and high specificity and high affinity of combination with the human serum albumin and stability and solubility of the antibody are maintained. The anti-human serum albumin nano antibody can be used for separation, purification and detection of human serum albumin and separation and purification of polypeptide, protein or antibody drugs fused with the anti-human serum albumin nano antibody. Meanwhile, the anti-human serum albumin nano-antibody can effectively prolong the half-life period of polypeptide, protein and antibody drugs fused with the anti-human serum albumin nano-antibody, and can be used for developing long-acting polypeptide, protein or antibody drugs.

The invention provides a solid-liquid combined synthesis method of semeglutide, which belongs to the technical field of semeglutide synthesis, and specifically comprises the following steps: segmenting a main chain of the semeglutide into three shorter polypeptide fragments, namely a fragment 4, a fragment 5 and a fragment 2 at sites 7-14, 15-22 and 23-37, and respectively synthesizing at the same time; performing solid-phase assembly on the fragment 4 and the fragment 5 to form 7-22 peptide fragments, namely a fragment 1, and after the fragment 1 is cut off from the resin, forming NHS ester at a C end; after the fragment 2 is assembled, selectively removing a protecting group A11oc on the Lys26, then connecting with a side chain for fatty acid treatment to form a fragment 3, and cutting off the fragment 3 from the resin; and connecting the NHS ester of the fragment 1 with the fragment 3 in a liquid phase reaction system. The crude semeglutide prepared by the synthetic method is relatively high in yield and purity. The refined semeglutide of which the purity is more than 99.3% and the content of single impurity is less than 0.1% can be obtained at high yield through a conventional purification means.

The invention provides a solid-phase synthesis method of semeglutide, and belongs to the technical field of synthesis of medical intermediates, and the method specifically comprises the following steps: segmenting a semeglutide main chain into three shorter polypeptide fragments, namely a fragment 4, a fragment 5 and a fragment 2, which are 7-14 sites, 15-22 sites and 23-37 sites; and respectively synthesizing and then assembling fragments to obtain a target product. The method specifically comprises the following steps: a) synthesizing a 7-14 peptide fragment and a 15-22 peptide fragment, and assembling the 7-14 peptide fragment and the 15-22 peptide fragment into a 7-22 peptide fragment, namely a fragment 1; b) synthesizing a 23-37 peptide fragment, selectively removing a protecting group A11oc on Lys26, and connecting with a side chain to form a fragment 3; c) connecting the peptide fragment 7-22 with the peptide fragment 23-37, and removing a protecting group to obtain a crude product; and d) separating and purifying to obtain a finished product. According to the invention, the purpose of high-purity, high-yield and low-cost synthesis of the semeglutide bulk drug can be achieved.

Crystalline forms of peptide fragments, methods for their preparation and their use in the preparation of peptides are provided. The crystalline compound of the present invention can be used as an intermediate having improved purity and physical properties for peptide synthesis.

The invention provides a preparation method of tiall peptide, and belongs to the technical field of polypeptide synthesis, according to the preparation method, a small amount of lysis solution is adopted for lysis, a small amount of poor solution composed of methyl tert-butyl ether and n-heptane with the volume ratio of 1-2: 1 is used for crude peptide precipitation, precipitated particles are uniform, large and not prone to caking, the crude peptide impurity level is lower, and the purity of the crude peptide is higher. The method has the advantages that the method is simple in process and easy in subsequent purification step, the amount of generated waste liquid is small, the activating agent 7-(1H-pyrrolo [2, 3-b] pyridine-1-yl)-1H-benzo [d] [1, 2, 3] triazole-1-alcohol is used for activating amino acid, the coupling reaction degree is high, and the target peptide yield is high. The preparation method of the tilpotide has the advantages of being simple, economical, capable of achieving mass production, low in impurity content, high in purification yield, high in yield and the like.

Linkers for linking a therapeutic agent to other moieties, such as an Fc region of an antibody. A linker having two or more maleimide functional groups, which may be subjected to a nucleophilic conjugate addition reaction. A method for increasing the duration of action of a therapeutic agent by linking a novel linker to the Fc region of an antibody. Antibody drug conjugates having a longer duration of action than the drug alone.

A GLP-1 / GIP dual-targeted polypeptide, containing a first polypeptide having the following amino acid sequence: X1X2X3GT FX4SDY SX5X6X7X8 X9X10X11X12X13 X14FX15X16W LX17X18X19. The GLP-1 / GIP dual-targeted polypeptide can effectively reduce the weight and blood sugar level.

The invention discloses a cell and a method for detecting the activity of a GLP-1R / GIPR double-target agonist drug. The invention relates to a cell for co-expressing GLP-1R, GIPR and CRE-miniP-luciferase reporter genes, and provides a method for detecting the biological activity of a GLP-1R / GIPR double-target agonist drug based on the cell, and the method is simple to operate, short in test period, sensitive in reaction, small in variability, strong in specificity and high in accuracy, can be used for release inspection of products, and can be used for detecting the biological activity of the GLP-1R / GIPR double-target agonist drug. The method has important significance on quality control and clinical application of GLP-1R / GIPR double-target agonist drugs.

The invention relates to the field of medicine synthesis, and discloses a GCG-GLP-1 dual agonist compound. The GCG-GLP-1 dual-agonist compound provided by the invention is used for preparing a pharmaceutical composition for treating diseases, and the application of the pharmaceutical composition in preparing a medicine for treating at least one of the following diseases, the diseases include type II diabetes mellitus, impaired glucose tolerance, type I diabetes mellitus, obesity, hypertension, metabolic syndrome, dyslipidemia, cognitive impairment, atherosclerosis, myocardial infarction, coronary heart disease, cardiovascular disease, stroke, inflammatory bowel syndrome and / or dyspepsia or gastric ulcer, hepatic fibrosis disease and pulmonary fibrosis disease.

The invention provides novel compounds which are peptide hormone analogues, and which are useful in treating disorders such as diabetes and obesity. The compounds of the general sequence recited in the specification possess a tailored profile with regards to potency properties at the GIP receptor. With regard to in vivo properties, administration of example peptides of the invention have been shown, in animal models, to result in increased weight loss. Preferred compounds achieve this without reducing food intake significantly.

The invention relates to the field of medicine synthesis, and discloses a GLP-1 / GIP / GCG tri-agonist compound. The GLP-1 / GIP / GCG three-agonist compound is used for preparing a medicine composition for treating diseases, and the application of the medicine composition in preparing a medicine for treating at least one of the following diseases, namely, the GLP-1 / GIP / GCG three-agonist compound, and the GLP-1 / GIP / GCG three-agonist compound. The diseases include type II diabetes mellitus, impaired glucose tolerance, type I diabetes mellitus, obesity, hypertension, metabolic syndrome, dyslipidemia, cognitive impairment, atherosclerosis, myocardial infarction, coronary heart disease, cardiovascular disease, stroke, inflammatory bowel syndrome and / or dyspepsia or gastric ulcer, hepatic fibrosis disease and pulmonary fibrosis disease.

The invention relates to the field of medicine synthesis, and discloses a GLP-1 / GIP / GCG tri-agonist compound. The GLP-1 / GIP / GCG three-agonist compound is used for preparing a medicine composition for treating diseases, and the application of the medicine composition in preparing a medicine for treating at least one of the following diseases, namely, the GLP-1 / GIP / GCG three-agonist compound, and the GLP-1 / GIP / GCG three-agonist compound. The diseases include type II diabetes mellitus, impaired glucose tolerance, type I diabetes mellitus, obesity, hypertension, metabolic syndrome, dyslipidemia, cognitive impairment, atherosclerosis, myocardial infarction, coronary heart disease, cardiovascular disease, stroke, inflammatory bowel syndrome and / or dyspepsia or gastric ulcer, hepatic fibrosis disease and pulmonary fibrosis disease.

To provide a more effective medicament which is potent in vitro and potent against weight loss, which at the same time does not result in proportionally increased levels of side effects, which has improved pharmacokinetic properties, which has improved chemical stability, which is suitable for once weekly administration in humans, and / or which is suitable for oral administration.SOLUTION: The present invention relates to a GLP-1- / GIP- / amylin-receptor tri-agonist. This GLP-1- / GIP- / amylin-receptor tri-agonist may have improved pharmacokinetic properties and may be suitable for once weekly administration. The invention also relates to pharmaceutical compositions comprising such a GLP-1- / GIP- / amylin-receptor tri-agonist. The tri-agonist and pharmaceutical compositions comprising it may be used as a medicament for the treatment of subjects with overweight, obesity and associated co-morbidity.SELECTED DRAWING: None

The invention relates to the field of biological medicine preparation, and provides a semi-synthesis preparation method of semeglutide and a preparation method of a semeglutide side chain, the semi-synthesis preparation method comprises the following steps: 1, in the presence of a first base catalyst, mixing a compound SMG-1 solution with a compound III solution, reacting to obtain a compound IV, and filtering to obtain a compound III; wherein the addition amount of the first base catalyst is such that the pH value of the SMG-1 solution is 11.2-11.6; 2, in the presence of a coupling agent and a second base catalyst, a compound IV solution and a compound SMG-3 solution are mixed and coupled to obtain a compound V, and the pH value in the step 2 is 9.5-10.0; and 3, carrying out deprotection on the compound V by using a deprotection agent to finally obtain the semeglutide. The method provided by the invention has the advantages of few reaction steps, reduced cost, high semeglutide purity and high yield, and is suitable for large-scale industrial production.

Provided are a GLP1 analogue and GLP1 / GIP receptor co-agonist analogues, a fusion protein comprising the GLP1 analogue or the GLP1 / GIP receptor co-agonist analogue, and methods of use thereof. In various embodiments, the fusion protein comprises the GLP1 analogue or the GLP1 / GIP receptor co-agonist analogue fused to a protecting antibody or further fused to a stabilizing domain. In some embodiments, the fusion proteins are useful for treating or ameliorating a symptom or indication of a disorder such as obesity and diabetes.

The present disclosure pertains to novel Glucagon like Peptide-1 (GLP-1) (7-37) analogs having an amino acid sequence with Leu or Ile at the C-terminal. The new analogs are potent GLP-1 agonists with reduced adverse effect and improved duration of action. The present disclosure further relates to acylated derivatives of the new analogs which have further improved potency and duration of action and are suitable for oral administration. The analogs of present disclosure may be useful in treatment of diabetes and obesity.

The invention relates to the field of medicine synthesis, and discloses a GLP-1 / GCG dual-agonist compound. The GLP-1 / GCG dual-agonist compound provided by the invention is used for preparing a pharmaceutical composition for treating diseases, and application of the pharmaceutical composition in preparation of a medicine for treating at least one of the following diseases, the diseases include type II diabetes mellitus, impaired glucose tolerance, type I diabetes mellitus, obesity, hypertension, metabolic syndrome, dyslipidemia, cognitive impairment, atherosclerosis, myocardial infarction, coronary heart disease, cardiovascular disease, stroke, inflammatory bowel syndrome and / or dyspepsia or gastric ulcer, hepatic fibrosis disease and pulmonary fibrosis disease.

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.

Incretin analogs are provided that have activity at each of the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptors. The incretin analogs have structural features resulting in balanced activity and extended duration of action at each of these receptors. Methods also are provided for treating diseases such as type 2 diabetes mellitus, dyslipidemia, metabolic syndrome, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and obesity.

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

Provided herein are monocistronic, bicistronic, and polycistronic expression constructs for the expression of gut peptides and pharmaceutical compositions comprising such expression constructs. Also provided are methods of using such expression constructs, for example, for inducing satiation in a subject in need thereof or for treating obesity in a subject in need thereof.

The invention provides semeglutide, which is synthesized by adopting the following method, and the specific steps are as follows: 1) segmenting the main chain of semeglutide into three polypeptide fragments: 7-14 sites, 15-22 sites and 23-37 sites; (2) respectively preparing the 7-14-site fragments, the 15-22-site fragments and the 23-37-site fragments through solid-phase synthesis; 3) connecting the 7-14-site fragment with the 15-22-site fragment to form a 7-22-site fragment, and activating the C end of the fragment into active ester; (4) selectively removing an Alloc protecting group of Lys26 in the 23-37-site fragment, and then carrying out fatty acid modification to obtain a modified 23-37-site fragment; 5) in a liquid phase system, coupling the activated 7-22-site fragment and the modified 23-37-site fragment according to a molar ratio of 1: (0.6-1.4) to form a complete polypeptide chain; and 6) removing the protecting group and purifying to obtain a semaglutide finished product. The method provided by the invention can effectively realize high-purity, high-yield and low-cost synthesis of the semeglutide bulk drug.

The invention relates to the technical field of polypeptide drugs for metabolic diseases, in particular to a glucagon-like peptide (GLP-1), a glucose-dependent insulinotropic polypeptide (GIP) and a glucagon (GCG) triple receptor agonist (protein). According to the triple receptor agonist protein provided by the technical scheme, weight reduction is achieved, meanwhile, lower side effects are shown, and drug compliance is enhanced. The triple receptor stimulant researched and developed by the technical scheme can be applied to preparation of medicines with the effects of losing weight, reducing lipid or reducing blood sugar, solves the technical problem that the existing GLP-1, GIP and GCG triple receptor stimulants are difficult to reduce side effects while reducing body weight, and breaks through the weight loss mode that the traditional medicines depend on appetite suppression; due to the unique action mechanism and good safety, a safer and more effective treatment scheme is provided for patients, and the medicine has wide market prospects and social benefits.

Described herein are methods of syntheses and therapeutic uses of covalently modified peptides and / or proteins. The covalently modified peptides and / or proteins allow for improved pharmaceutical properties of peptide and protein-based therapeutics.

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.