Peptide derivatives of exendin-4
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-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.
1. 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, of the formula exendin-4 (1-39)-A, wherein exendin 4 (1-39) corresponds to a sequence identity of over 90% to the amino acid sequence of
(SEQ ID NO 3)
H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-
1 2 3 4 5 6 7 8 9 10 11 12
Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-
13 14 15 16 17 18 19 20 21 22 23 24
Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-
25 26 27 28 29 30 31 32 33 34 35 36
Pro-Pro-Ser-NH 2 ;
37 38 39
with A being an attachment group, which is located at the C-terminus and represents a lysine, and wherein a chelator is coupled with the attachment group A for the labeling with radionuclides.
2. Peptide derivatives from exendin-4 according to the claim 1 , wherein the chelator is N,N-Bis(2-[bis(carboxymethyl)amino]-ethyl)glycine), DOTA (1,4,7,10-Tetraazacyclodo-decane-1,4,7,10-tetra-acetic acid), HYNIC (6-Hydrazinopyridin-3-carbonic acid), MAG3 (mercaptoacetyl-glycylglycylglycine), N4 (1,4,8,11-tetraazaundecane).
3. Peptide derivatives from exendin-4 according to the claim 1 , wherein the chosen radionuclide is in particular from the group F-18, Cu-64, Cu-67, Ga-67, Ga-68, Y-86, Y-90, Tc-99m, In-111, I-123, I-124, I-131, Lu-177, Re-186, Re-188, Pt-193m, Pt-195m, Ac-225, At-211, Bi-213, Sm-153 or Er-169.
4. Agent for the diagnostic and therapy of benign and malignant diseases, in which GLP-1 receptor expression plays a role, wherein it contains labeled peptide derivatives of exendin-4 according to claim 1 .
5. Agent according to claim 4 wherein the labeled peptide derivatives contain a radionuclide.
6. Agent according to the claim 5 , wherein after labeling with radionuclides for in vitro applications, free bonding sites are saturated with nat InCL 3 .
7. Peptide derivatives from extendin-4 according to claim 2 , wherein the chelator is DTPA (Diethylenetriaminepentaacetic acid).