Control of amylin agglomeration is of interest for both the study of pathophysiology and the design of amylin-based pharmaceutical products. Here we report the effects of a large set of common buffering agents, aminoacids and nucleoside phosphates over the amylin amyloid aggregation. Circular dichroism showed no apparent effects of the co-solutes over the secondary-structure of soluble amylin. Instead, we found a large dependence of the fibrillation process on the total amount of co-solute charged groups. The amyloid nature of the aggregates was confirmed by transmission electron microscopy, X-ray diffraction and infrared spectroscopy. While acidic pH and low-ionic co-solutes shows the largest size effect in hampering aggregation, no further effect was observed that could identify a single compound as a major direct heterotropic determinants of the amyloid process. These data suggest a more physico-chemical effect of co-solutes over the modulation of amylin instead of a chemical entity-related causal factor.

中文翻译：

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小分子对胰岛淀粉样多肽原纤维的异向调节：对配方设计的启示。

控制胰岛淀粉样多肽团聚对于病理生理学研究和基于胰岛淀粉样多肽的药物产品的设计都是有意义的。在这里，我们报告了一大批常见的缓冲剂，氨基酸和磷酸核苷对胰岛淀粉样淀粉样蛋白聚集的影响。圆二色性显示共溶质对可溶性胰岛淀粉样多肽的二级结构没有明显影响。相反，我们发现原纤化过程对共溶质带电基团的总量有很大的依赖性。聚集体的淀粉样性质通过透射电子显微镜，X射线衍射和红外光谱确认。酸性pH和低离子共溶质在阻碍聚集方面显示出最大的尺寸效应，没有观察到进一步的影响，可以确定单一化合物是淀粉样蛋白过程的主要直接异向决定因素。这些数据表明，共溶质对胰岛淀粉样多肽的调节具有更大的物理化学作用，而不是与化学实体相关的因果关系。