Carrey E A, Epand R M
Int J Pept Protein Res. 1983 Sep;22(3):362-70. doi: 10.1111/j.1399-3011.1983.tb02103.x.
The 29 amino acid polypeptide hormone glucagon was cleaved into two large fragments by the enzyme clostripain. The conformational properties of these two fragments were monitored by circular dichroism at pH 2 and 12 in both the presence and absence of sodium dodecyl sulfate. Both glucagon (1-17) and glucagon (19-29) have reduced abilities to fold in aqueous solution. However, both fragments can take on structure of higher apparent helical content in acidic solution in the presence of sodium dodecyl sulfate but only the glucagon (19-29) retains this conformation at high pH. Neither of the two fragments react with dimyristoylphosphatidylcholine as the intact peptide does. Only the carboxyl terminal fragment was capable of reacting with an antibody specific for glucagon. The glucagon (1-17) has markedly reduced affinity for binding to the glucagon receptor as well as markedly reduced ability to stimulate adenylate cyclase activity which is not affected by the presence of glucagon (19-29). It is proposed that the intact sequence provides specific groups required for activity as well as the potential for forming a stable amphipathic helix, both of which are necessary for full biological activity at low peptide concentrations.
29个氨基酸的多肽激素胰高血糖素被梭菌蛋白酶切割成两个大片段。在有和没有十二烷基硫酸钠存在的情况下，于pH 2和12条件下通过圆二色性监测这两个片段的构象性质。胰高血糖素（1-17）和胰高血糖素（19-29）在水溶液中的折叠能力均降低。然而，在十二烷基硫酸钠存在下，两个片段在酸性溶液中都能呈现出更高表观螺旋含量的结构，但只有胰高血糖素（19-29）在高pH下仍保持这种构象。这两个片段都不像完整肽那样与二肉豆蔻酰磷脂酰胆碱发生反应。只有羧基末端片段能够与针对胰高血糖素的特异性抗体发生反应。胰高血糖素（1-17）与胰高血糖素受体结合的亲和力显著降低，刺激腺苷酸环化酶活性的能力也显著降低，而胰高血糖素（19-29）的存在对此没有影响。有人提出，完整序列提供了活性所需的特定基团以及形成稳定两亲螺旋的潜力，这两者对于低肽浓度下的完全生物活性都是必需的。
