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Insulin Complexation with Cyclodextrins—A Molecular Modeling Approach

Around 5% of the population of the world is affected with the disease called diabetes mellitus. The main medication of the diabetes is the insulin; the active form is the insulin monomer, which is an instable molecule, because the long storage time, or the high temperature, can cause the monomer ins...

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Autores principales: Bucur, Pálma, Fülöp, Ibolya, Sipos, Emese
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778189/
https://www.ncbi.nlm.nih.gov/pubmed/35056780
http://dx.doi.org/10.3390/molecules27020465
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author Bucur, Pálma
Fülöp, Ibolya
Sipos, Emese
author_facet Bucur, Pálma
Fülöp, Ibolya
Sipos, Emese
author_sort Bucur, Pálma
collection PubMed
description Around 5% of the population of the world is affected with the disease called diabetes mellitus. The main medication of the diabetes is the insulin; the active form is the insulin monomer, which is an instable molecule, because the long storage time, or the high temperature, can cause the monomer insulin to adapt an alternative fold, rich in β-sheets, which is pharmaceutically inactive. The aim of this study is to form different insulin complexes with all the cyclodextrin used for pharmaceutical excipients (native cyclodextrin, methyl, hydroxyethyl, hydroxypropyl and sulfobutylether substituted β-cyclodextrin), in silico condition, with the AutoDock molecular modeling program, to determine the best type of cyclodextrin or cyclodextrin derivate to form a complex with an insulin monomer, to predict the molar ratio, the conformation of the complex, and the intermolecular hydrogen bonds formed between the cyclodextrin and the insulin. From the results calculated by the AutoDock program it can be predicted that insulin can make a stable complex with 5–7 molecules of hydroxypropyl-β-cyclodextrin or sulfobutylether-β-cyclodextrin, and by forming a complex potentially can prevent or delay the amyloid fibrillation of the insulin and increase the stability of the molecule.
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spelling pubmed-87781892022-01-22 Insulin Complexation with Cyclodextrins—A Molecular Modeling Approach Bucur, Pálma Fülöp, Ibolya Sipos, Emese Molecules Article Around 5% of the population of the world is affected with the disease called diabetes mellitus. The main medication of the diabetes is the insulin; the active form is the insulin monomer, which is an instable molecule, because the long storage time, or the high temperature, can cause the monomer insulin to adapt an alternative fold, rich in β-sheets, which is pharmaceutically inactive. The aim of this study is to form different insulin complexes with all the cyclodextrin used for pharmaceutical excipients (native cyclodextrin, methyl, hydroxyethyl, hydroxypropyl and sulfobutylether substituted β-cyclodextrin), in silico condition, with the AutoDock molecular modeling program, to determine the best type of cyclodextrin or cyclodextrin derivate to form a complex with an insulin monomer, to predict the molar ratio, the conformation of the complex, and the intermolecular hydrogen bonds formed between the cyclodextrin and the insulin. From the results calculated by the AutoDock program it can be predicted that insulin can make a stable complex with 5–7 molecules of hydroxypropyl-β-cyclodextrin or sulfobutylether-β-cyclodextrin, and by forming a complex potentially can prevent or delay the amyloid fibrillation of the insulin and increase the stability of the molecule. MDPI 2022-01-11 /pmc/articles/PMC8778189/ /pubmed/35056780 http://dx.doi.org/10.3390/molecules27020465 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bucur, Pálma
Fülöp, Ibolya
Sipos, Emese
Insulin Complexation with Cyclodextrins—A Molecular Modeling Approach
title Insulin Complexation with Cyclodextrins—A Molecular Modeling Approach
title_full Insulin Complexation with Cyclodextrins—A Molecular Modeling Approach
title_fullStr Insulin Complexation with Cyclodextrins—A Molecular Modeling Approach
title_full_unstemmed Insulin Complexation with Cyclodextrins—A Molecular Modeling Approach
title_short Insulin Complexation with Cyclodextrins—A Molecular Modeling Approach
title_sort insulin complexation with cyclodextrins—a molecular modeling approach
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778189/
https://www.ncbi.nlm.nih.gov/pubmed/35056780
http://dx.doi.org/10.3390/molecules27020465
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