The Role of Salt Bridge Formation in Glucagon: An Experimental and Theoretical Study of Glucagon Analogs and Peptide Fragments of Glucagon

Table 1 Pharmacological parameters of cyclic analogues of glucagon

	Receptor Binding Activity		Adenylyl Cyclase
Glucagon and Analogues	Relative Affinity^a, (%)	Fold Decrease	Relative Potency^b, (%)	Maximum Activity^c (%)	pA₂^d Value
1A Glucagon	100		100	100	—
1B Glucagon amide	100		15	100	—
1C DesHis¹glucagon	8	12.5	0.1	36	—
1D DesHis¹glucagon amide	63	1.6	0.16	44	—
2 Cyclic[Glu²Lys⁵]-amide	0.41	244	0.58	100
3 Cyclic[Glu⁹Lys¹²]-amide	4.8	21	0.126	18	—
4 DesHis¹cyclic[Glu⁹ Lys¹²]-amide	12.6	8	<0.00013	—	6.9
5 DesHis¹Glu⁹cyclic[Glu²⁰ Lys²⁴]-amide	19.1	5.3	<0.003	—	6.8

^aThe ratio of unlabeled glucagon concentration required to displace 50% of receptor-bound [¹²⁵I]-glucagon, IC₅₀, to the concentration required for analogues of glucagon × 100.
^bThe ratio of glucagon concentration at 50% stimulation (EC₅₀) of natural glucagon to that of glucagon analogue × 100.
^cThe ratio of maximum response of glucagon analogue to that of natural glucagon × 100.
^dpA₂ value is the negative logarithm of the concentration of inhibitor that reduces the response to 1 unit of agonist to the response obtained from 0.5 unit of agonist.

ISSN: 1528-3658