Search for New Aggregable Fragments of Human Insulin

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-pepti...

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Main Authors: Monika Swiontek, Justyna Fraczyk, Joanna Wasko, Agata Chaberska, Lukasz Pietrzak, Zbigniew J. Kaminski, Lukasz Szymanski, Slawomir Wiak, Beata Kolesinska
Format: Article
Language:English
Published: MDPI AG 2019-04-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/24/8/1600
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spelling doaj-9ac252dcb72a455e8ccc4c970c2c8a742020-11-24T22:19:07ZengMDPI AGMolecules1420-30492019-04-01248160010.3390/molecules24081600molecules24081600Search for New Aggregable Fragments of Human InsulinMonika Swiontek0Justyna Fraczyk1Joanna Wasko2Agata Chaberska3Lukasz Pietrzak4Zbigniew J. Kaminski5Lukasz Szymanski6Slawomir Wiak7Beata Kolesinska8Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, PolandInstitute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, PolandInstitute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, PolandInstitute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, PolandInstitute of Mechatronics and Information Systems, Faculty of Electrical, Electronic, Computer and Control Engineering, Lodz University of Technology, Stefanowskiego 18/22, 90-924 Lodz, PolandInstitute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, PolandInstitute of Mechatronics and Information Systems, Faculty of Electrical, Electronic, Computer and Control Engineering, Lodz University of Technology, Stefanowskiego 18/22, 90-924 Lodz, PolandInstitute of Mechatronics and Information Systems, Faculty of Electrical, Electronic, Computer and Control Engineering, Lodz University of Technology, Stefanowskiego 18/22, 90-924 Lodz, PolandInstitute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, PolandIn 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<sup>-</sup>) 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.https://www.mdpi.com/1420-3049/24/8/1600Aggregationamyloid depositsamyloid-like fiber formationdiabetesSPPStriazine coupling reagents
collection DOAJ
language English
format Article
sources DOAJ
author Monika Swiontek
Justyna Fraczyk
Joanna Wasko
Agata Chaberska
Lukasz Pietrzak
Zbigniew J. Kaminski
Lukasz Szymanski
Slawomir Wiak
Beata Kolesinska
spellingShingle Monika Swiontek
Justyna Fraczyk
Joanna Wasko
Agata Chaberska
Lukasz Pietrzak
Zbigniew J. Kaminski
Lukasz Szymanski
Slawomir Wiak
Beata Kolesinska
Search for New Aggregable Fragments of Human Insulin
Molecules
Aggregation
amyloid deposits
amyloid-like fiber formation
diabetes
SPPS
triazine coupling reagents
author_facet Monika Swiontek
Justyna Fraczyk
Joanna Wasko
Agata Chaberska
Lukasz Pietrzak
Zbigniew J. Kaminski
Lukasz Szymanski
Slawomir Wiak
Beata Kolesinska
author_sort Monika Swiontek
title Search for New Aggregable Fragments of Human Insulin
title_short Search for New Aggregable Fragments of Human Insulin
title_full Search for New Aggregable Fragments of Human Insulin
title_fullStr Search for New Aggregable Fragments of Human Insulin
title_full_unstemmed Search for New Aggregable Fragments of Human Insulin
title_sort search for new aggregable fragments of human insulin
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2019-04-01
description 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<sup>-</sup>) 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.
topic Aggregation
amyloid deposits
amyloid-like fiber formation
diabetes
SPPS
triazine coupling reagents
url https://www.mdpi.com/1420-3049/24/8/1600
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