Properties of amidinated glucagons.
Porcine glucagon has been reacted with a series of alkyl imidates. The epsilon-amino group and both the alpha and epsilon-amino groups were modified and the subsequent glucagon derivatives were purified by ion-exchange chromatography and characterized. The modified glucagons were compared with native glucagon in their ability to activate hepatic adenylate cyclase and to compete with 125I-glucagon for binding to sites specific for glucagon in hepatic plasma membranes. N epsilon-acetamidino-glucagon was as biologically potent, in both activity and binding, as native glucagon, whereas N epsilon-4-hydroxyphenylamidinoglucagon required a twofold higher concentration to obtain similar levels. These findings suggest that modification through the epsilon-amino group with alkyl imidates possessing reporter groups should result in glucagon derivatives with significant biological potency, thus providing a new approach to the study of this peptide hormone. Amidination of both epsilon and alpha-amino groups resulted in glucagon derivatives which were agonists with respect to adenylate cyclase activation and which displayed unexpected anomylous behavior on chromatography.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000578:Amidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002462:Cell Membrane / Q000201:enzymology; D005934:Glucagon / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D051381:Rats; D013552:Swine
D000578:Amidines; D000596:Amino Acids; D005934:Glucagon; D000262:Adenylyl Cyclases