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First Experimental Quantitative Charge Density Studies of Advanced Intermediate of Vitamin D Analogues
Vitamins D are a group of fat-soluble secosteroids which play a regulatory role in the functioning of most cells. Rational design of new vitamin D analogs, of increased therapeutic potency and lowered calcemic side effects, requires high-resolution initial structures and a deep understanding of inte...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951618/ https://www.ncbi.nlm.nih.gov/pubmed/35335121 http://dx.doi.org/10.3390/molecules27061757 |
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author | Wanat, Monika Malinska, Maura Kutner, Andrzej Woźniak, Krzysztof |
author_facet | Wanat, Monika Malinska, Maura Kutner, Andrzej Woźniak, Krzysztof |
author_sort | Wanat, Monika |
collection | PubMed |
description | Vitamins D are a group of fat-soluble secosteroids which play a regulatory role in the functioning of most cells. Rational design of new vitamin D analogs, of increased therapeutic potency and lowered calcemic side effects, requires high-resolution initial structures and a deep understanding of interactions with the molecular targets. In this paper, using quantum crystallography, we present the first determination of the experimental quantitative charge density of an advanced intermediate of vitamin D analogues as well as a reconstruction of the theoretical electron density of final vitamin D analogues. Application of these methods allows for topological and electrostatic interaction energy analysis. We showed that the A-ring chair conformation has a significant influence on the topological properties of vitamin D compounds. Moreover, the interactions between the CD-ring and side-chain additionally stabilize the crystal structure. These results are supported by our theoretical calculations and previous biological studies. |
format | Online Article Text |
id | pubmed-8951618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89516182022-03-26 First Experimental Quantitative Charge Density Studies of Advanced Intermediate of Vitamin D Analogues Wanat, Monika Malinska, Maura Kutner, Andrzej Woźniak, Krzysztof Molecules Article Vitamins D are a group of fat-soluble secosteroids which play a regulatory role in the functioning of most cells. Rational design of new vitamin D analogs, of increased therapeutic potency and lowered calcemic side effects, requires high-resolution initial structures and a deep understanding of interactions with the molecular targets. In this paper, using quantum crystallography, we present the first determination of the experimental quantitative charge density of an advanced intermediate of vitamin D analogues as well as a reconstruction of the theoretical electron density of final vitamin D analogues. Application of these methods allows for topological and electrostatic interaction energy analysis. We showed that the A-ring chair conformation has a significant influence on the topological properties of vitamin D compounds. Moreover, the interactions between the CD-ring and side-chain additionally stabilize the crystal structure. These results are supported by our theoretical calculations and previous biological studies. MDPI 2022-03-08 /pmc/articles/PMC8951618/ /pubmed/35335121 http://dx.doi.org/10.3390/molecules27061757 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 Wanat, Monika Malinska, Maura Kutner, Andrzej Woźniak, Krzysztof First Experimental Quantitative Charge Density Studies of Advanced Intermediate of Vitamin D Analogues |
title | First Experimental Quantitative Charge Density Studies of Advanced Intermediate of Vitamin D Analogues |
title_full | First Experimental Quantitative Charge Density Studies of Advanced Intermediate of Vitamin D Analogues |
title_fullStr | First Experimental Quantitative Charge Density Studies of Advanced Intermediate of Vitamin D Analogues |
title_full_unstemmed | First Experimental Quantitative Charge Density Studies of Advanced Intermediate of Vitamin D Analogues |
title_short | First Experimental Quantitative Charge Density Studies of Advanced Intermediate of Vitamin D Analogues |
title_sort | first experimental quantitative charge density studies of advanced intermediate of vitamin d analogues |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951618/ https://www.ncbi.nlm.nih.gov/pubmed/35335121 http://dx.doi.org/10.3390/molecules27061757 |
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