Table 261 Glucagon analogs with various amino acid replaceme

Table 26.1: Glucagon analogs with various amino acid replacements. Binding affinity refers to the ability of the glucagon analog to bind to hepatic membrane receptors. Activity was measured by testing each analog\'s ability to stimulate CAMP production as compared to native glucagon. The des prefix indicates that the specified amino acid has been deleted. (Based on Unson, et al., 1994 and 1998.) Binding affinity of maximum activity Glucagon analog 100% 100% Glucagon 45% Des-Asp 8.3% 54% Ne ace 12 47 90.5 59.7 Ala12 17.3 12 114 85.7 Glu12 80.4 Ala17 30 Leu Glu17 94.8 21.3 13 Ala18 94.4 Leu. 56 Glu 18 100 Des-His 63 Des-His\'-Des-Asp Des-His -Lys9 Des-His1-Glu12 0.11 28 Des-His -Glu17 21.5 18 Des-Hisi-Glu18 0.44

Solution

For the designing of the glucagon antagonist we have to take some points in consideration like:

Those glucagon analogs which shows better binding to hepatic membrane receptors and lacking of ability to stimulate cAMP production can be a glucagon antagonist. In the above analogs Des-His¹-Lys⁹ shows 70% binding affinity and 0% cAMP activation activity can be act as a glucagon antagonist.

For becoming a antagonist molecule should contain good binding affinity towards its receptor and block the action of that receptor.

Here the name of some glucagon analogs those can be a antagonist:

Des-Asp⁹ : binding affinity= 45% and cAMP Activation activity= 8.3%

Lys^9: binding affinity= 54% and cAMP Activation activity= 0%

Des-His¹-Lys⁹ :binding affinity= 70% and cAMP Activation activity= 0%