Properties of Amidinated Glucagons

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Abstract
Porcine glucagon was 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; N.epsilon.-4-hydroxyphenylamidinoglucagon required a 2-fold higher concentration to obtain similar levels. Apparently 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 partial agonists with respect to adenylate cyclase activation and which displayed unexpected anomylous behavior on chromatography.