Two different insulin analogues, insulin degludec and lithocholyl insulin, were studied by small-angle X-ray scattering with respect to their self-assembly and interactions in solution at different concentrations of insulin and salt, NaCl. Very different behavior was observed for the two. Insulin degludec, linked to a hexadecanedioic acid, consistently formed di-hexamers, without any further oligomeric growth upon screening of electrostatic repulsions, indicating a stable di-hexamer unit without further oligomerization, as expected in the presence of phenol. The other insulin analogue, linked to the sterol lithocholic acid, formed n-hexamers with n ranging from 1 to 15, increasing with NaCl concentration and insulin concentration, indicating attractive forces in competition with the electrostatic repulsion and solution entropy. At the highest concentration of insulin and NaCl, a liquid crystal phase was observed, which has not previously been identified, featuring a quadratic structure organized into layers, which might hold interesting properties for pharmaceutical applications.

中文翻译：

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药学相关胰岛素类似物的低聚化可通过小角 X 射线散射揭示不同浓度和盐度

两种不同的胰岛素类似物，德谷胰岛素和石胆基胰岛素，通过小角 X 射线散射研究了它们在不同浓度的胰岛素和盐、NaCl 的溶液中的自组装和相互作用。观察到两者的行为非常不同。与十六烷二酸连接的德谷胰岛素始终形成二六聚体，在筛选静电排斥时没有任何进一步的低聚体生长，表明在苯酚存在下没有进一步低聚化的稳定二六聚体单元。与甾醇石胆酸相连的另一种胰岛素类似物与n-六聚体形成从 1 到 15，随 NaCl 浓度和胰岛素浓度而增加，表明吸引力与静电排斥和溶液熵竞争。在胰岛素和 NaCl 的最高浓度下，观察到了一个液晶相，这是以前没有发现的，具有组织成层的二次结构，这可能具有制药应用的有趣特性。