| 摘要 |
PROBLEM TO BE SOLVED: To provide modified glucagon peptides having enhanced potency at the glucagon receptor relative to native glucagon.SOLUTION: Further modification of the glucagon peptides by forming lactam bridges or substituting a terminal carboxylic acid with an amide group produces peptides exhibiting glucagon/GLP-1 receptor co-agonist activity. The solubility and stability of these high potency glucagon analogs can be further improved by modification of the polypeptides by pegylation, substitution of carboxy terminal amino acids, or addition of a peptide selected from the group consisting of sequence GPSSGAPPPS, sequence K-RNRNNIA and sequence KRNR to a carboxy terminal. |
