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Synthesis and biological activity of α-l-fucosyl ceramides, analogues of the potent agonist, α-d-galactosyl ceramide KRN7000

Several l-fucoglycolipids are associated with diseases such as cancer, cystic fibrosis and rheumatoid arthritis. Activation of iNKT cells is known to lead to the production of cytokines that can help alleviate or exacerbate these conditions. α-Galactosyl ceramide (α-GalCer) is a known agonist of iNK...

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Autores principales: Veerapen, Natacha, Reddington, Faye, Bricard, Gabriel, Porcelli, Steven A., Besra, Gurdyal S.
Formato: Texto
Lenguaje:English
Publicado: Elsevier Science Ltd 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957807/
https://www.ncbi.nlm.nih.gov/pubmed/20462758
http://dx.doi.org/10.1016/j.bmcl.2010.04.079
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author Veerapen, Natacha
Reddington, Faye
Bricard, Gabriel
Porcelli, Steven A.
Besra, Gurdyal S.
author_facet Veerapen, Natacha
Reddington, Faye
Bricard, Gabriel
Porcelli, Steven A.
Besra, Gurdyal S.
author_sort Veerapen, Natacha
collection PubMed
description Several l-fucoglycolipids are associated with diseases such as cancer, cystic fibrosis and rheumatoid arthritis. Activation of iNKT cells is known to lead to the production of cytokines that can help alleviate or exacerbate these conditions. α-Galactosyl ceramide (α-GalCer) is a known agonist of iNKT cells and it is believed that its fucosyl counterpart might have similar immunogenic properties. We herein report the synthesis of α-l-fucosyl ceramide derivatives and describe their biological evaluation. The key challenge in the synthesis of the target molecules involved the stereoselective synthesis of the α-glycosidic linkage. Of the methods examined, the per-TMS-protected glycosyl iodide donor was completely α-selective, and could be scaled up to provide gram quantities of the azide precursor 11, from which a range of N-acylated α-l-fucosyl ceramides were readily obtained and evaluated for ex vivo expansion of human iNKT cells.
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spelling pubmed-29578072010-10-21 Synthesis and biological activity of α-l-fucosyl ceramides, analogues of the potent agonist, α-d-galactosyl ceramide KRN7000 Veerapen, Natacha Reddington, Faye Bricard, Gabriel Porcelli, Steven A. Besra, Gurdyal S. Bioorg Med Chem Lett Article Several l-fucoglycolipids are associated with diseases such as cancer, cystic fibrosis and rheumatoid arthritis. Activation of iNKT cells is known to lead to the production of cytokines that can help alleviate or exacerbate these conditions. α-Galactosyl ceramide (α-GalCer) is a known agonist of iNKT cells and it is believed that its fucosyl counterpart might have similar immunogenic properties. We herein report the synthesis of α-l-fucosyl ceramide derivatives and describe their biological evaluation. The key challenge in the synthesis of the target molecules involved the stereoselective synthesis of the α-glycosidic linkage. Of the methods examined, the per-TMS-protected glycosyl iodide donor was completely α-selective, and could be scaled up to provide gram quantities of the azide precursor 11, from which a range of N-acylated α-l-fucosyl ceramides were readily obtained and evaluated for ex vivo expansion of human iNKT cells. Elsevier Science Ltd 2010-06-01 /pmc/articles/PMC2957807/ /pubmed/20462758 http://dx.doi.org/10.1016/j.bmcl.2010.04.079 Text en © 2010 Elsevier Ltd. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Article
Veerapen, Natacha
Reddington, Faye
Bricard, Gabriel
Porcelli, Steven A.
Besra, Gurdyal S.
Synthesis and biological activity of α-l-fucosyl ceramides, analogues of the potent agonist, α-d-galactosyl ceramide KRN7000
title Synthesis and biological activity of α-l-fucosyl ceramides, analogues of the potent agonist, α-d-galactosyl ceramide KRN7000
title_full Synthesis and biological activity of α-l-fucosyl ceramides, analogues of the potent agonist, α-d-galactosyl ceramide KRN7000
title_fullStr Synthesis and biological activity of α-l-fucosyl ceramides, analogues of the potent agonist, α-d-galactosyl ceramide KRN7000
title_full_unstemmed Synthesis and biological activity of α-l-fucosyl ceramides, analogues of the potent agonist, α-d-galactosyl ceramide KRN7000
title_short Synthesis and biological activity of α-l-fucosyl ceramides, analogues of the potent agonist, α-d-galactosyl ceramide KRN7000
title_sort synthesis and biological activity of α-l-fucosyl ceramides, analogues of the potent agonist, α-d-galactosyl ceramide krn7000
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957807/
https://www.ncbi.nlm.nih.gov/pubmed/20462758
http://dx.doi.org/10.1016/j.bmcl.2010.04.079
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