Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
Institute of Mechatronics and Information Systems, Faculty of Electrical, Electronic, Computer and Control Engineering, Lodz University of Technology, Stefanowskiego 18/22, 90-924 Lodz, Poland.
Molecules. 2019 Apr 23;24(8):1600. doi: 10.3390/molecules24081600.
In this study, three independent methods were used to identify short fragment of both chains of human insulin which are prone for aggregation. In addition, circular dichroism (CD) research was conducted to understand the progress of aggregation over time. The insulin fragments (deca- and pepta-peptides) were obtained by solid-phase synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TosO) as a coupling reagent. Systematic studies allowed identification of the new fragments, expected to be engaged in triggering aggregation of the entire structure of human insulin under physiological conditions. It was found that the aggregation process occurs through various structural conformers and may favor the formation of a fibrous structure of aggregate.
在这项研究中,使用了三种独立的方法来鉴定易于聚集的人胰岛素两条链的短片段。此外,还进行了圆二色性(CD)研究,以了解随时间推移的聚集过程。胰岛素片段(十肽和肽)是通过固相合成获得的,使用 4-(4,6-二甲氧基-1,3,5-三嗪-2-基)-4-甲基吗啉鎓对甲苯磺酸酯(DMT/NMM/TosO)作为偶联试剂。系统研究确定了新的片段,这些片段有望在生理条件下引发人胰岛素整个结构的聚集。结果发现,聚集过程通过各种结构构象发生,并可能有利于聚集的纤维状结构的形成。