Search for New Aggregable Fragments of Human Insulin
Monika Swiontek,
Justyna Fraczyk,
Joanna Wasko,
Agata Chaberska,
Lukasz Pietrzak,
Zbigniew J. Kaminski,
Lukasz Szymanski,
Slawomir Wiak,
Beata Kolesinska
Affiliations
Monika Swiontek
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland
Justyna Fraczyk
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland
Joanna Wasko
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland
Agata Chaberska
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland
Lukasz Pietrzak
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
Zbigniew J. Kaminski
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland
Lukasz Szymanski
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
Slawomir Wiak
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
Beata Kolesinska
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland
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.
