Modified exedins and uses thereof
View Patent ↗Novel exendins with modifications at one or more of following positions: 2, 14, 27 or 28 and polyethylene glycol derivatives thereof are provided. These compounds are useful in treating type 2 diabetes as GLP-1 receptor agonists.
1. A modified exendin selected from a peptide that comprises any one of the amino acid sequences of SEQ ID Nos. 88, 89, 95 and 96.
2. A modified exendin or pharmaceutically acceptable salt thereof that comprises the amino acid sequence of SEQ ID No. 95 and polyethylene glycol (PEG) wherein the PEG has a molecular weight (MW) between 20,000 and 60,000 daltons.
3. The modified exendin of claim 2 , wherein the MW of said PEG is 40,000 dalton.
4. The modified exendin of claim 3 , wherein the modification is obtained by connecting the polyethylene glycol and the regiospecific group at the carboxyl terminal end of the peptide.
5. A method for treatment of type 2 diabetes, comprising administration of an effective dosage of a modified exendin or pharmaceutically acceptable salt thereof that comprises the amino acid sequence of SEQ ID No. 95 and polyethylene glycol (PEG) wherein the PEG has a molecular weight (MW) between 20,000 and 60,000 daltons to a patient in need thereof.
6. The method of claim 5 , wherein the MW of said PEG is 40,000 dalton.
7. The method of claim 6 , wherein the modification is obtained by connecting the polyethylene glycol and the regiospecific group at the carboxyl terminal end of the peptide.
8. A method for the reduction of blood glucose in a mammal comprising administration of an effective dosage of a modified exendin or a pharmaceutically acceptable salt thereof, to the mammal, wherein the modified exendin comprises the amino acid sequence of SEQ ID No. 95 and polyethylene glycol (PEG), and wherein the PEG has a molecular weight (MW) between 20,000 and 60,000 daltons.
9. The method of claim 8 , wherein the PEG has a molecular weight (MW) of 40,000 dalton.
10. The method of claim 9 , wherein the modification is obtained by connecting the polyethylene glycol and the regiospecific group at the carboxyl terminal end of the peptide.
11. A method for preparation of modified exendin or a pharmaceutically acceptable salt thereof, which comprises the amino acid sequence of SEQ ID No. 95 and polyethylene glycol (PEG) wherein the PEG has a molecular weight (MW) between 20,000 and 60,000 daltons, comprising solid phase and liquid-phase synthesis, reverse-phase high performance liquid chromatography, ion-exchange and gel filtration for purification or lyophilization.
12. The method of claim 11 wherein the PEG has a molecular weight (MW) of 40,000 dalton.
13. The method of claim 12 , wherein the modification is obtained by connecting the polyethylene glycol and the regiospecific group at the carboxyl terminal end of the peptide.