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

doi:10.3390/molecules24081600

Search for New Aggregable Fragments of Human Insulin

Molecules. 2019 Apr 23;24(8):1600. doi: 10.3390/molecules24081600.

Authors

Monika Swiontek¹, Justyna Fraczyk², Joanna Wasko³, Agata Chaberska⁴, Lukasz Pietrzak⁵, Zbigniew J Kaminski⁶, Lukasz Szymanski⁷, Slawomir Wiak⁸, Beata Kolesinska⁹

Affiliations

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.

MeSH terms

Amino Acid Sequence
Humans
Indicators and Reagents / chemistry
Insulin / chemistry*
Kinetics
Oligopeptides / chemical synthesis
Oligopeptides / chemistry*
Peptide Fragments / chemical synthesis
Peptide Fragments / chemistry*
Peptide Fragments / ultrastructure
Protein Aggregates*
Solid-Phase Synthesis Techniques / methods
Solutions
Thermodynamics
Triazines / chemistry

Substances

Indicators and Reagents
Insulin
Oligopeptides
Peptide Fragments
Protein Aggregates
Solutions
Triazines

Grants and funding

project number UMO-2015/19/B/ST8/02594/National Science Centre, Poland