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Preparation, Supramolecular Aggregation and Immunological Activity of the Bona Fide Vaccine Adjuvant Sulfavant S
In aqueous conditions, amphiphilic bioactive molecules are able to form self-assembled colloidal structures modifying their biological activity. This behavior is generally neglected in preclinical studies, despite its impact on pharmacological development. In this regard, a significative example is...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551793/ https://www.ncbi.nlm.nih.gov/pubmed/32872423 http://dx.doi.org/10.3390/md18090451 |
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author | Manzo, Emiliano Fioretto, Laura Gallo, Carmela Ziaco, Marcello Nuzzo, Genoveffa D’Ippolito, Giuliana Borzacchiello, Assunta Fabozzi, Antonio De Palma, Raffaele Fontana, Angelo |
author_facet | Manzo, Emiliano Fioretto, Laura Gallo, Carmela Ziaco, Marcello Nuzzo, Genoveffa D’Ippolito, Giuliana Borzacchiello, Assunta Fabozzi, Antonio De Palma, Raffaele Fontana, Angelo |
author_sort | Manzo, Emiliano |
collection | PubMed |
description | In aqueous conditions, amphiphilic bioactive molecules are able to form self-assembled colloidal structures modifying their biological activity. This behavior is generally neglected in preclinical studies, despite its impact on pharmacological development. In this regard, a significative example is represented by a new class of amphiphilic marine-inspired vaccine adjuvants, collectively named Sulfavants, based on the β-sulfoquinovosyl-diacylglyceride skeleton. The family includes the lead product Sulfavant A (1) and two epimers, Sulfavant R (2) and Sulfavant S (3), differing only for the stereochemistry at C-2 of glycerol. The three compounds showed a significant difference in immunological potency, presumably correlated with change of the aggregates in water. Here, a new synthesis of diastereopure 3 was achieved, and the study of the immunomodulatory behavior of mixtures of 2/3 proved that the bizarre in vitro response to 1–3 effectively depends on the supramolecular aggregation states, likely affecting the bioavailability of agonists that can effectively interact with the cellular targets. The evidence obtained with the mixture of pure Sulfavant R (2) and Sulfavant S (3) proves, for the first time, that supramolecular organization of a mixture of active epimers in aqueous solution can bias evaluation of their biological and pharmacological potential. |
format | Online Article Text |
id | pubmed-7551793 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75517932020-10-14 Preparation, Supramolecular Aggregation and Immunological Activity of the Bona Fide Vaccine Adjuvant Sulfavant S Manzo, Emiliano Fioretto, Laura Gallo, Carmela Ziaco, Marcello Nuzzo, Genoveffa D’Ippolito, Giuliana Borzacchiello, Assunta Fabozzi, Antonio De Palma, Raffaele Fontana, Angelo Mar Drugs Article In aqueous conditions, amphiphilic bioactive molecules are able to form self-assembled colloidal structures modifying their biological activity. This behavior is generally neglected in preclinical studies, despite its impact on pharmacological development. In this regard, a significative example is represented by a new class of amphiphilic marine-inspired vaccine adjuvants, collectively named Sulfavants, based on the β-sulfoquinovosyl-diacylglyceride skeleton. The family includes the lead product Sulfavant A (1) and two epimers, Sulfavant R (2) and Sulfavant S (3), differing only for the stereochemistry at C-2 of glycerol. The three compounds showed a significant difference in immunological potency, presumably correlated with change of the aggregates in water. Here, a new synthesis of diastereopure 3 was achieved, and the study of the immunomodulatory behavior of mixtures of 2/3 proved that the bizarre in vitro response to 1–3 effectively depends on the supramolecular aggregation states, likely affecting the bioavailability of agonists that can effectively interact with the cellular targets. The evidence obtained with the mixture of pure Sulfavant R (2) and Sulfavant S (3) proves, for the first time, that supramolecular organization of a mixture of active epimers in aqueous solution can bias evaluation of their biological and pharmacological potential. MDPI 2020-08-29 /pmc/articles/PMC7551793/ /pubmed/32872423 http://dx.doi.org/10.3390/md18090451 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Manzo, Emiliano Fioretto, Laura Gallo, Carmela Ziaco, Marcello Nuzzo, Genoveffa D’Ippolito, Giuliana Borzacchiello, Assunta Fabozzi, Antonio De Palma, Raffaele Fontana, Angelo Preparation, Supramolecular Aggregation and Immunological Activity of the Bona Fide Vaccine Adjuvant Sulfavant S |
title | Preparation, Supramolecular Aggregation and Immunological Activity of the Bona Fide Vaccine Adjuvant Sulfavant S |
title_full | Preparation, Supramolecular Aggregation and Immunological Activity of the Bona Fide Vaccine Adjuvant Sulfavant S |
title_fullStr | Preparation, Supramolecular Aggregation and Immunological Activity of the Bona Fide Vaccine Adjuvant Sulfavant S |
title_full_unstemmed | Preparation, Supramolecular Aggregation and Immunological Activity of the Bona Fide Vaccine Adjuvant Sulfavant S |
title_short | Preparation, Supramolecular Aggregation and Immunological Activity of the Bona Fide Vaccine Adjuvant Sulfavant S |
title_sort | preparation, supramolecular aggregation and immunological activity of the bona fide vaccine adjuvant sulfavant s |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551793/ https://www.ncbi.nlm.nih.gov/pubmed/32872423 http://dx.doi.org/10.3390/md18090451 |
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