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Molecules. 2019 Apr 23;24(8). pii: E1600. doi: 10.3390/molecules24081600.

Search for New Aggregable Fragments of Human Insulin.

Author information

1
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland. monika.swiontek@gmail.com.
2
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland. justyna.fraczyk@p.lodz.pl.
3
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland. joanna.wasko@p.lodz.pl.
4
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland. agata.chaberska@p.lodz.pl.
5
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. lukasz.pietrzak@p.lodz.pl.
6
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland. zbigniew.kaminski@p.lodz.pl.
7
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. lukasz.szymanski@p.lodz.pl.
8
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@p.lodz.pl.
9
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland. beata.kolesinska@p.lodz.pl.

Abstract

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.

KEYWORDS:

Aggregation; SPPS; amyloid deposits; amyloid-like fiber formation; diabetes; triazine coupling reagents

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