Peptide derivatives of exendin-4
AssigneePhilipps-Universitat Marburg
InventorsMartin GOTTHARDT, Martin Béhé, Thomas Behr, Burkhard J. Göke
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Abstract
In the current invention peptides, which are derived from GLP-1 (glucagon-like peptide-1) and exendin-3 and/or exendin-4, are provided which bond to the GLP-1 receptor and can be used, labeled or unlabeled, for the production of an agent for diagnostic and therapy of benign and malignant diseases, in which GLP-1 receptor expression plays a role.
Claims45
Peptide derivatives of GLP-1 and exendin-3, wherein their C-terminus is modified by an amine and wherein their N-terminus binds to the GLP-1 receptor.
Chimeric peptides from GLP-1 and exendin, with exendin being exendin 3, wherein they contain completely or in part the amino acid sequences of the peptides
- GLP-1 (1-37)
- H-His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-
- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
- Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-
- 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33
- Lys-Gly-Arg-Gly-OH
- 34 35 36 37
- and exendin-3:
- H-His-Ser-Asp-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-
- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
- Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-
- 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
- Pro-Pro-Pro-Ser-NH2
- 36 37 38 39.
Use of peptide derivatives from exendin-4, wherein their C-terminus is modified by an amine and wherein their N-terminus binds to the GLP-1 receptor, with a sequence identity of over 90% to the amino acid sequence of exendin-4:
- H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-
- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
- Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-
- 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
- Pro-Pro-Pro-Ser-NH2
- 36 37 38 39
- wherein the peptide derivatives are based on exendin-4 (1-39)A,
- with A being an attachment group comprising of one or more amino acids or its derivatives as a signal molecule, or to bond signal molecules or to stabilize them, which is located at the C-terminus and represents an amine, wherein a chelator is coupled with attachment group A for the labeling with radionuclides for the production of an agent for diagnostic and therapy of benign and malignant diseases, in which the GLP-1 receptor expression plays a role.
Application of peptide derivatives from exendin-4, wherein their C-terminus is modified by an amine and wherein their N-terminus binds to the GLP-1 receptor, with a sequence identity of over 90% to the amino acid sequence of exendin-4:
- H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-
- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
- Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-
- 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
- Pro-Pro-Pro-Ser-NH2
- 36 37 38 39
- wherein the peptide derivatives are based on exendin-4 (1-39)A,
- with A being an attachment group comprising of one or more amino acids or its derivatives as a signal molecule, or to bond signal molecules or to stabilize them, which is located at the C-terminus and represents an amine, wherein a chelator is coupled with attachment group A for the labeling with radionuclides in order to determine the density of insulin producing cells in a tissue.
Application of peptide derivatives from exendin-4, wherein their C-terminus is modified by an amine and wherein their N-terminus binds to the GLP-1 receptor, with a sequence identity of over 90% to the amino acid sequence of exendin-4:
- H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-
- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
- Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-
- 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
- Pro-Pro-Pro-Ser-NH2
- 36 37 38 39
- wherein the peptide derivatives are based on exendin-4 (1-39)A,
- with A being an attachment group comprising of one or more amino acids or its derivatives as a signal molecule, or to bond signal molecules or to stabilize them, which is located at the C-terminus and represents an amine, wherein a chelator is coupled with attachment group A for the labeling with radionuclides in order to determine the expression of GLP-1 receptors or their density.
Use of an agent for diagnostic and therapy of benign and malignant diseases, in which GLP-1 receptor expression plays a role, wherein the agent contains labeled peptide derivatives of exendin-4, wherein their C-terminus is modified by an amine and wherein their N-terminus binds to the GLP-1 receptor, with a sequence identity of over 90% to the amino acid sequence of exendin-4:
- H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-
- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
- Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-
- 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
- Pro-Pro-Pro-Ser-NH2
- 36 37 38 39
- wherein the peptide derivatives are based on exendin-4 (1-39)A,
- with A being an attachment group comprising of one or more amino acids or its derivatives as a signal molecule, or to bond signal molecules or to stabilize them, which is located at the C-terminus and represents an amine, wherein a chelator is coupled with attachment group A for the labeling with radionuclides.
Use of an agent for diagnostic and therapy of neuroendocrine tumors (NET), particularly insulinomas and small cell bronchial carcinomas, wherein the agent contains labeled peptide derivatives from exendin-4, wherein their C-terminus is modified by an amine and wherein their N-terminus binds to the GLP-1 receptor, with a sequence identity of over 90% to the amino acid sequence of exendin-4:
- H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-
- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
- Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-
- 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
- Pro-Pro-Pro-Ser-NH2
- 36 37 38 39
- wherein the peptide derivatives are based on exendin-4 (1-39)A,
- with A being an attachment group comprising of one or more amino acids or its derivatives as a signal molecule, or to bond signal molecules or to stabilize them, which is located at the C-terminus and represents an amine, wherein a chelator is coupled with attachment group A for the labeling with radionuclides.
Use of an agent in scintigraphy, PET, SPECT, MRI, optical diagnostic, receptor-mediated chemotherapy, receptor-mediated, cytostatic or cytotoxic therapy and radiopeptide therapy, wherein the agent contains labeled peptide derivatives of exendin-4, wherein their C-terminus is modified by an amine and wherein their N-terminus binds to the GLP-1 receptor, with a sequence identity of over 90% to the amino acid sequence of exendin-4:
- H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-
- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
- Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-
- 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
- Pro-Pro-Pro-Ser-NH2
- 36 37 38 39
- wherein the peptide derivatives are based on exendin-4 (1-39)A,
- with A being an attachment group comprising of one or more amino acids or its derivatives as a signal molecule, or to bond signal molecules or to stabilize them, which is located at the C-terminus and represents an amine, wherein a chelator is coupled with attachment group A for the labeling with radionuclides.
Use of an agent for diagnostic and therapy of benign and malignant diseases, in which GLP-1 receptor expression plays a role, wherein the agent contains unlabeled peptide derivatives from exendin-4, wherein their C-terminus is modified by an amine and wherein their N-terminus binds to the GLP-1 receptor, with a sequence identity of over 90% to the amino acid sequence of exendin-4:
- H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-
- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
- Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-
- 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
- Pro-Pro-Pro-Ser-NH2
- 36 37 38 39
- wherein the peptide derivatives are based on exendin-4 (1-39)A,
- with A being an attachment group comprising of one or more amino acids or its derivatives as a signal molecule, or to bond signal molecules or to stabilize them, which is located at the C-terminus and represents an amine, wherein a chelator is coupled with attachment group A for the labeling with radionuclides.
Use of an agent for diagnostic and therapy of neuroendocrine tumors (NET), particularly insulinomas and small cell bronchial carcinomas, wherein the agent contains unlabeled peptide derivatives from exendin-4, wherein their C-terminus is modified by an amine and wherein their N-terminus binds to the GLP-1 receptor, with a sequence identity of over 90% to the amino acid sequence of exendin-4:
- H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-
- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
- Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-
- 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
- Pro-Pro-Pro-Ser-NH2
- 36 37 38 39
- wherein the peptide derivatives are based on exendin-4 (1-39)A,
- with A being an attachment group comprising of one or more amino acids or its derivatives as a signal molecule, or to bond signal molecules or to stabilize them, which is located at the C-terminus and represents an amine, wherein a chelator is coupled with attachment group A for the labeling with radionuclides.
Dependencies are inferred from the claim text.