| abstract |
Modified glucagon peptides are revealed exhibiting increased activity in the glucagon receptor compared to native glucagon. Another modification of glucagon peptides, such as forming an intramolecular bridge without a covalent bond, and optionally replacing the terminal carboxylic acid with an amide group, produces peptides that exhibit a glucagon / GLP-1 receptor coagonist activity. The solubility and stability of these high potency glucagon analogs can also be improved by modification of the polypeptides by pegylation, substitution of the carboxyterminal amino acids or the addition of a carboxyterminal peptide selected from the group consisting of SEQ ID Ns: 26 (GPSSGAPPPS ), SEQ ID Ns: 27 (KRNRNNIA) and SEQ ID Ns: 28 (KRNR). |