Hybrid polypeptides with selectable properties

FIELD: medicine.

SUBSTANCE: present invention concerns new, selectable hybrid polypeptides expressing at least two hormonal activities containing a first biologically active module of a peptide hormone covalently bonded with at least one additional biologically active module of the peptide hormone.

EFFECT: polypeptides can be used as agents for treatment and prevention of metabolic diseases and disorders associated with overweight.

19 cl, 6 dwg, 6 tbl, 4 ex

 

The text descriptions are given in facsimile form.

1. Hybrid polypeptide exhibiting at least two hormonal activity, containing the first biologically active peptide hormone module, covalently linked by at least one before Amiternum biologically active peptide hormone module,
where the biologically active peptide hormone modules are independently selected from the group consisting of: a complex of peptide hormones, fragments of complex peptide hormones, exhibiting at least one hormonal activity of a complex of peptide hormones, analogs and derivatives of complex peptide hormones, exhibiting at least one hormonal activity of a complex of peptide hormones, fragments, analogs and derivatives of complex peptide hormones, exhibiting at least one hormonal activity of a complex of peptide hormones;
complex peptide hormones independently selected from at least two of the groups consisting of: Amylin, adrenomedullin (ADM), calcitonin (CT), peptide encoded by the genome of calcitonin (CGRP), intermedin, cholecystokinin ("CCK"), leptin, peptide YY (PYY), glucagon-like peptide-1 (GLP-1), glucagon-like peptide 2 (GLP-2), oxyntomodulin (OHM) and Asendin-4; and
both of biologically active module peptide hormones exhibit at least one hormonal activity of its complex peptide hormone; and where optional:
in the case when at least one biologically active peptide hormone module exhibiting at least one hormonal activity of a complex of the peptide hormone, is an Amylin, a fragment of Amylin that manifests on minicamera one hormonal activity, analogue or derivative Amylin, exhibiting at least one hormonal activity, or a fragment, analogue or derivative Amylin, exhibiting at least one hormonal activity, and at least one other biologically active peptide hormone module is a CCK, a fragment of the FCS, exhibiting at least one hormonal activity, an analogue or derivative SSK exhibiting at least one hormonal activity, a fragment, analog or derivative SSK exhibiting at least one hormonal activity, ART, fragment, ARTICLE, showing at least one hormonal activity, an analogue or derivative ART showing at least one hormonal activity, or a fragment, analogue or derivative ART, exhibiting at least one hormonal activity, in this case, the hybrid polypeptide further comprises at least three biologically active module peptide hormone selected from at least three different complex peptide hormones.

2. A hybrid polypeptide according to claim 1, characterized in that at least one of the first biologically active peptide hormone module or at least one additional biologically active peptide hormone module is a complex peptide hormone or fragments is complex peptide hormone, displaying at least one hormonal activity of a complex of the peptide hormone.

3. A hybrid polypeptide according to claim 1, characterized in that at least one of the first biologically active peptide hormone module or at least one additional biologically active peptide hormone module is an analog or derivative of a complex peptide hormone exhibiting at least one hormonal activity, or a fragment, analogue or derivative of complex peptide hormone exhibiting at least one hormonal activity of a complex of the peptide hormone.

4. A hybrid polypeptide according to claim 1, characterized in that the complex peptide hormones independently selected from the group consisting of: Amylin, calcitonin, CCK, PYY and essendine-4.

5. A hybrid polypeptide according to claim 1, characterized in that at least one biologically active peptide hormone module exhibiting at least one hormonal activity, located on the N-terminal part of the hybrid polypeptide is inserted into the structure in orientation from the C-end N-end.

6. A hybrid polypeptide according to claim 5, characterized in that the N-end of the hybrid polypeptide amitirova.

7. A hybrid polypeptide according to claim 1, characterized in that at least one biologically active peptide hormone module, showing p is at least one hormonal activity, located on the C-terminal part of the hybrid polypeptide.

8. A hybrid polypeptide according to claim 7, characterized in that the end of the hybrid polypeptide amitirova.

9. A hybrid polypeptide according to claim 1, characterized in that the end of one biologically active peptide hormone module is directly attached to the N-end of the at least one additional biologically active peptide hormone module with the formation of covalent binding.

10. A hybrid polypeptide according to claim 1, characterized in that the biologically active modules peptide hormone covalently attached using one or more linker groups independently selected from the group consisting of: Akilov; dicarboxylic acids PEG; amino acids; polyaminoacid; bifunctional linkers; aminocaproyl (Asa), β-alanyl, 8-amino-3,6-dioxaoctyl and Gly-Lys-Arg (GKR).

11. A hybrid polypeptide according to claim 1, wherein the first biologically active peptide hormone module is selected from the group consisting of: essendine-4, a fragment of essendine-4 showing at least one hormonal activity, an analogue or derivative of essendine-4 showing at least one hormonal activity, and fragment analog of essendine-4 showing at least one hormonal activity; and
at least one additional bi is logically active peptide hormone module nazwisko selected from the group consisting of: Amylin, Amylin fragment exhibiting at least one hormonal activity, an analogue or derivative Amylin, exhibiting at least one hormonal activity, or a fragment of Amylin analogue, showing at least one hormonal activity, SSK, fragment SSK exhibiting at least one hormonal activity, an analogue or derivative SSK exhibiting at least one hormonal activity, a fragment of a similar SSK exhibiting at least one hormonal activity, ARTICLE, section, ARTICLE exhibiting at least one hormonal activity, an analogue or derivative ART, exhibiting at least one hormonal activity, a fragment of a similar ARTICLE, showing at least one hormonal activity, and peptide enhancer.

12. A hybrid polypeptide according to claim 11, wherein the first biologically active peptide hormone module is selected from the group consisting of: essendine-4, essendine-4(1-27), essendine-4(1-28),14Leu,25Phe-accendino-4(1-28);5Ala,14Leu,25Phe-accendino-4(1-28) and14leu-accendino-4(1-28); and at least one additional biologically active peptide hormone module is independently selected from the group consisting of:25,28,29Pro-h-Amylin, h-Amylin-(1-7)-14Gln,11,18Arg-sCT(8-27)-Amylin-(33-37, h-Amylin-(1-7)-11,18Arg-sCt(8-32)-h-Amylin(33-37),1des-Lys-h-Amylin-(1-7),11,18Arg-sCt(8-32)-h-Amylin(33-37), CCK-8, Phe2CCK-8.

13. A hybrid polypeptide according to claim 11, wherein the hybrid polypeptide comprises at least three biologically active module peptide hormones.

14. A hybrid polypeptide according to claim 11, wherein the hybrid polypeptide contains at least four biologically active module peptide hormones.

15. A hybrid polypeptide according to claim 11, wherein the first biologically active peptide hormone module is located on the C-end of the hybrid polypeptide, and at least one additional biologically active peptide hormone module is located on the N-end of the hybrid polypeptide.

16. A hybrid polypeptide according to claim 11, wherein the first biologically active peptide hormone module is located on the N-end of the hybrid polypeptide, and at least one additional biologically active peptide hormone module is located on the C-end of the hybrid polypeptide.

17. A hybrid polypeptide according to claim 4, characterized in that the complex peptide hormones independently selected from at least two of the group consisting of: Amylin and essendine-4.

18. A hybrid polypeptide according to 17, characterized in that the module of the peptide hormone Amylin is located on the C-conceiving polypeptide.

19. A hybrid polypeptide according to 17, characterized in that the module peptide hormone actedin is located on the N-end of the hybrid polypeptide.



 

Same patents:

FIELD: medicine.

SUBSTANCE: in dissolvent, which contains from 55% to 70% of water (wt/wt), precursor of insulin or precursor of insulin derivative is exposed to fermentative splitting at alkaline values of pH. In process of fermentative splitting, they use tripsin or lysil-specific protease, preferably Achromobacter lyticus protease I. Then without separation of intermediate product from reaction mixture, mentioned intermediate product is fermentatively complemented with nucleophilic compound, which represents aminoacid ether, aminoacid amide, peptide, peptide ether or peptide amide in reaction mixture, having water content in the range from 10% to 50% of water (wt/wt), at acidic values of pH, close to neutral pH value. If required, protective group (s) is/are removed.

EFFECT: preparation of insulin compound from its precursor by efficient improved method.

24 cl, 5 ex

FIELD: medicine.

SUBSTANCE: recombinant strain Escherichia coli is produced, which contains plasmid pHINS21 (Escherichia coli JM109/ pHINS21), defining synthesis of hybrid protein, made of N-terminal fragment of human gamma-interferon and human proinsulin, joined by peptide linker, which contains site of splitting with enterokinase (Asp4Lys). Yield of hybrid product that includes proinsulin, provided with new strain-producer, makes at least 30% of total amount of cell protein. Method is suggested for preparation of human proinsulin, including cultivation of strain-producer Escherichia coli JM109/pHINS21, separation of inclusion bodies and their dissolution, renaturation of hybrid protein and its cleaning with ion-exchange chromatography, splitting of hybrid protein with enterokinase or its catalytic subunit and cleaning of proinsulin by ion-exchange chromatography on sorbates with sulfprofile groups.

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4 cl, 4 dwg, 5 ex

FIELD: medicine.

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6 cl, 1 dwg, 4 tbl, 5 ex

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FIELD: medicine.

SUBSTANCE: invention concerns derivatives of a misinformation (B30) human insulin which have lateral a chain, attached to ε-amino group of the rest of the lysine which is present at the B-chain of initial insulin where this lateral the chain has the general formula: -W-X-Y-Z where W, X, Y and Z are such as it is defined in the description.

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15 cl, 4 tbl, 37 ex

FIELD: chemistry, pharmaceutics.

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17 cl, 2 tbl, 8 ex

FIELD: biotechnology, in particular medical and biological industry.

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9 cl, 10 dwg, 6 tbl, 5 ex

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6 ex

The invention relates to biotechnology and can be used to obtain a properly curled, containing the precursor of insulin chimeric protein

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6 cl, 7 dwg, 4 tbl, 14 ex

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17 cl, 2 tbl, 8 ex

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3 cl, 3 ex, 3 dwg

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10 cl, 1 tbl, 411 ex

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Analogues of glp-1 // 2214418
The invention relates to peptide analogs glucoheptonate peptide-1 formula

(R2R3)-A7-A8-A9-A10-A11-A12-A13-A14-A15-A16-A17-A18-A19-A20-A21-A22-AND23-AND24-AND25-AND26-AND27-AND28-AND29-AND30-AND31-AND32-AND33-AND34-AND35-AND36-AND37-AND38-AND39-R1the values of the radicals indicated in the claims

Analogues of glp-1 // 2208015
The invention relates to compounds of the formula (R2R3) AND7-AND8-AND9-AND10-AND11-AND12-AND13-AND14-AND15-AND16-AND17-AND18-AND19-AND20-AND21-AND22-AND23-AND24-AND25-AND26-AND27-AND28-AND29-AND30-AND31-AND32-AND33-AND34-AND35-AND36-AND37-R1,

where a7-AND37represent different amino acid residues, the values radicals cm

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