Synthesis of truncated analogues of the iNKT cell agonist, α-galactosyl ceramide (KRN7000), and their biological evaluation

Stimulation of iNKT cells by α-galactosyl ceramide (α-GalCer), also known as KRN7000, and its truncated analogue OCH induces both Th1- and Th2-cytokines, with OCH inducing a Th2-cytokine bias. Skewing of the iNKT cells’ response towards either a Th1- or Th2-cytokine profile offers potential therapeu...

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Autores principales: Veerapen, Natacha, Reddington, Faye, Salio, Mariolina, Cerundolo, Vincenzo, Besra, Gurdyal S.
Formato: Texto
Lenguaje:English
Publicado: Elsevier Science 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052434/
https://www.ncbi.nlm.nih.gov/pubmed/21145749
http://dx.doi.org/10.1016/j.bmc.2010.11.032
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author Veerapen, Natacha
Reddington, Faye
Salio, Mariolina
Cerundolo, Vincenzo
Besra, Gurdyal S.
author_facet Veerapen, Natacha
Reddington, Faye
Salio, Mariolina
Cerundolo, Vincenzo
Besra, Gurdyal S.
author_sort Veerapen, Natacha
collection PubMed
description Stimulation of iNKT cells by α-galactosyl ceramide (α-GalCer), also known as KRN7000, and its truncated analogue OCH induces both Th1- and Th2-cytokines, with OCH inducing a Th2-cytokine bias. Skewing of the iNKT cells’ response towards either a Th1- or Th2-cytokine profile offers potential therapeutic benefits. The length of both the acyl and the sphingosine chains in α-galactosyl ceramides is known to influence the cytokine release profile. We have synthesized analogues of α-GalCer with truncated sphingosine chains for biological evaluation, with particular emphasis on the Th1/Th2 distribution. Starting from a common precursor, d-lyxose, the sphingosine derivatives were synthesised via a straightforward Wittig condensation.
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spelling pubmed-30524342011-04-12 Synthesis of truncated analogues of the iNKT cell agonist, α-galactosyl ceramide (KRN7000), and their biological evaluation Veerapen, Natacha Reddington, Faye Salio, Mariolina Cerundolo, Vincenzo Besra, Gurdyal S. Bioorg Med Chem Article Stimulation of iNKT cells by α-galactosyl ceramide (α-GalCer), also known as KRN7000, and its truncated analogue OCH induces both Th1- and Th2-cytokines, with OCH inducing a Th2-cytokine bias. Skewing of the iNKT cells’ response towards either a Th1- or Th2-cytokine profile offers potential therapeutic benefits. The length of both the acyl and the sphingosine chains in α-galactosyl ceramides is known to influence the cytokine release profile. We have synthesized analogues of α-GalCer with truncated sphingosine chains for biological evaluation, with particular emphasis on the Th1/Th2 distribution. Starting from a common precursor, d-lyxose, the sphingosine derivatives were synthesised via a straightforward Wittig condensation. Elsevier Science 2011-01-01 /pmc/articles/PMC3052434/ /pubmed/21145749 http://dx.doi.org/10.1016/j.bmc.2010.11.032 Text en © 2011 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
Salio, Mariolina
Cerundolo, Vincenzo
Besra, Gurdyal S.
Synthesis of truncated analogues of the iNKT cell agonist, α-galactosyl ceramide (KRN7000), and their biological evaluation
title Synthesis of truncated analogues of the iNKT cell agonist, α-galactosyl ceramide (KRN7000), and their biological evaluation
title_full Synthesis of truncated analogues of the iNKT cell agonist, α-galactosyl ceramide (KRN7000), and their biological evaluation
title_fullStr Synthesis of truncated analogues of the iNKT cell agonist, α-galactosyl ceramide (KRN7000), and their biological evaluation
title_full_unstemmed Synthesis of truncated analogues of the iNKT cell agonist, α-galactosyl ceramide (KRN7000), and their biological evaluation
title_short Synthesis of truncated analogues of the iNKT cell agonist, α-galactosyl ceramide (KRN7000), and their biological evaluation
title_sort synthesis of truncated analogues of the inkt cell agonist, α-galactosyl ceramide (krn7000), and their biological evaluation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052434/
https://www.ncbi.nlm.nih.gov/pubmed/21145749
http://dx.doi.org/10.1016/j.bmc.2010.11.032
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