927results about "Glucagons" patented technology

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.

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.

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 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 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 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.

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.

The present invention provides a pharmaceutical composition comprising a polypeptide or a pharmaceutically acceptable salt thereof. The polypeptide or the pharmaceutically acceptable salt thereof comprises the N-terminus of an amino acid sequence as shown in X1-Aib-X2, wherein X1 is a natural or unnatural amino acid residue comprising an imidazole group, and X2 is a natural or unnatural amino acid residue comprising an imidazole group. The pharmaceutical composition has good chemical stability.

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

Provided are a GLP-1GIP analog, an FGF21 protein, a trifunctional protein, and use thereof. The trifunctional protein comprises the GLP-1 / GIP analog and the FGF21 protein. Further provided is use of the GLP-1 / GIP analog, the FGF21 protein, and the trifunctional protein in the preparation of a drug for preventing and / or treating diseases related to GLP-1, GIP, and / or FGF21. The provided GLP-1 / GIP analog, FGF21 protein, and trifunctional protein can synergistically regulate blood glucose and lipid levels in vivo, meet multiple needs in patients with type 2 diabetes, including lowering blood glucose, alleviating hepatic steatosis, promoting weight loss, ameliorating circulating lipid metabolism disorder, etc., and have better biological safety and tolerability and longer in vivo half-lives.

The invention belongs to the technical field of biological medicine. The invention relates to a signal peptide, in particular to a signal peptide of GLP-1 and an analogue thereof and application thereof. The invention provides a signal peptide of a GLP-1 protein or an analogue thereof. The amino acid sequence of the signal peptide is shown as any one of SEQ ID NO.1-8. The signal peptide of the GLP-1 protein is improved, so that the signal peptide can promote the generation of an inclusion body and optimize the property of the inclusion body, and also can improve the unit yield of the target protein, and finally, the target protein can obtain more efficient expression. Besides, while the signal peptide is truncated, the base sequence of the target protein is optimized, the character of the inclusion body is changed, and the character of the inclusion body is further optimized. When the fusion protein is used for preparing the GLP-1 protein analogue, the proportion of the target protein in an inclusion body can be greatly improved while the original high inclusion body yield is ensured, the purpose of improving the productivity from the source is finally achieved, and the fusion protein has good application prospects and value.

The invention discloses a GLP-1 GIP analogue, an FGF21 protein, a three-function protein and an application thereof. The trifunctional protein comprises a GLP-1 / GIP analogue and an FGF21 (Fibroblast Growth Factor 21) protein. The invention also discloses application of the GLP-1 / GIP analogue, the FGF21 protein and the three-function protein in preparation of medicines for preventing and / or treating diseases related to GLP-1, GIP and / or FGF21. The GLP-1 / GIP analogue, the FGF21 protein and the three-function protein provided by the invention can synergistically regulate blood sugar and lipid levels in vivo, meet multiple requirements of patients with type 2 diabetes for reducing blood sugar, relieving liver fatty degeneration, reducing weight, improving circulating lipid metabolism disorder and the like, and are better in biological safety and tolerance and longer in in-vivo half-life period.

The invention belongs to the technical field of biomedical engineering, and particularly relates to a polypeptide preparation method for preparing a GLP-1 analogue through tandem expression. According to the method, a coding gene sequence of the GLP-1 analogue is repeatedly connected in series for a plurality of times, and then expression preparation is carried out on the basis of a genetic engineering technology. The inventor optimizes a series-connected polypeptide structure by adding a section of key peptide sequence. The key peptide serving as a leading peptide can greatly improve the expression quantity of the strain in the fermentation expression process; as a linked peptide, the key peptide sequence can effectively improve the recognition capability of enzyme digestion sites on one hand and can adjust the overall isoelectric point of the sequence on the other hand, so that the solubility, enzyme digestion yield and purity of a target product can be improved. Preliminary experiment results show that the expression quantity of the polypeptide prepared through expression is extremely high, the enzyme digestion efficiency is good, the good enzyme digestion efficiency can be achieved under the condition that the enzyme dosage is low, and the yield and purity of the final GLP-1 analogue are high.

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.

A dual function protein is disclosed. The dual function protein may be prepared by linking a biologically active protein and an FGF mutant protein to an Fc region of an immunoglobulin. The dual function protein has improved pharmacological efficacy, in vivo duration and protein stability. The dual function protein exhibits improved pharmacological efficacy, in vivo duration and protein stability. A pharmaceutical composition containing the dual function protein as an active ingredient may be effectively used as a therapeutic agent for diabetes, obesity, dyslipidemia, metabolic syndrome, non-alcoholic fatty liver diseases, non-alcoholic steatohepatitis or cardiovascular diseases.

The invention discloses a preparation method of semeglutide, which comprises the following steps: respectively using 8-bit and 12-bit single pseudo-proline serine in a combined manner, using 1-2-bit, 3-4-bit, 5-6-bit and 29-30-bit dipeptide fragments in a combined manner, using 27-29-bit and 14-16-bit 2, 4-dimethoxy benzyl modified glycine tripeptide fragments in a combined manner, and further comprising a 20-bit lysine fragment with a side chain group, the method is used for synthesizing semeglutide resin, and the semeglutide resin is cracked and purified to obtain the semeglutide. The preparation method combining the fragments is beneficial to completing solid phase coupling of the semeglutide, greatly improves the substitution value of the semeglutide peptide resin and the purity and yield of a crude product, remarkably reduces the purification difficulty of the crude product, finally reduces the synthesis cost, and is beneficial to industrial mass production.

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 present application relates to the field of medicine, and specifically to a GLP-1 analog fusion protein and its application. The GLP-1 analog fusion protein is obtained by fusing GLP-1 to the N-terminus of the IgG4 heavy chain constant region and the light chain constant region. The results of the study showed that the GLP-1 analog fusion protein of the present application has a significant effect on reducing the weight of mice. The volume and weight of the mouse liver decreased, and the NAS score and hepatic steatosis were significantly improved. Therefore, the present invention can be applied to drugs or products for weight loss or the treatment of fatty liver.

The present invention belongs to the technical field of purification of polypeptide drugs, and specifically relates to a method for purifying tilpotide, comprising: (a) preparing a crude tilpotide solution using an acetonitrile aqueous solution; (b) selecting a specific stationary phase, mobile phase, and elution gradient to purify the crude tilpotide solution for a first time to obtain a first fraction; (c) selecting a specific stationary phase, mobile phase, and elution gradient to purify the first fraction for a second time to obtain a second fraction; (d) performing nanofiltration concentration, salt exchange, filtration sterilization, and lyophilization on the second fraction to obtain the tilpotide product. The product obtained by the purification method of the present invention has a purity of more than 99.5%, and the total recovery rate of purification is more than 80%. The single-needle elution cycle of the present invention is only 35 to 40 minutes, which greatly reduces the use of organic solvents in the purification process of tilpotide, reduces purification costs, and is more environmentally friendly in the long term.

The invention relates to the technical field of polypeptide drug preparation methods, and provides a preparation method of retaglutide and a preparation method of a retaglutide intermediate.The preparation method of the retaglutide comprises the steps that a fragment 1-resin is prepared through a solid-phase synthesis method, then a fragment 2 and the fragment 1-resin are coupled through the solid-phase synthesis method, and the retaglutide is obtained. And cracking the retaglutide-resin, so as to obtain the retaglutide. Wherein the fragment 1 is a 15th-39th amino acid polypeptide fragment, and the fragment 2 is a 1st-14th amino acid polypeptide fragment. According to the preparation method disclosed by the invention, the production cost of the retaglutide can be greatly reduced, the synthesis steps are few, the subsequent treatment is simple, and the purity and the yield of the retaglutide are improved.

The invention relates to pharmaceutical compositions comprising a peptide, such as a GLP-1 peptide and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid. The invention further relates to processes for the preparation of such compositions, and their use in medicine.

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.

To provide a protein to be used for treating metabolic disorders, and a method for treating the metabolic disorders.SOLUTION: Provided is a method of treating metabolic diseases and disorders using an antigen binding protein specific to GIPR polypeptide. In various embodiments, the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels, and diabetic nephropathy. In a specific embodiment, the antigen binding protein is administered in combination with GLP-1 receptor agonist.SELECTED DRAWING: None