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6?-derivatised ?-galcer analogues capable of inducing strong CD1d-mediated Th1-biased NKT cell responses in mice

6?-derivatised ?-galcer analogues capable of inducing strong CD1d-mediated Th1-biased NKT cell responses in mice
6?-derivatised ?-galcer analogues capable of inducing strong CD1d-mediated Th1-biased NKT cell responses in mice
?-Galactosyl ceramide (?-GalCer, also known as KRN 7000) is known as the prototypical antigen for invariant natural killer T (NKT) cells. Stimulation of NKT cells by CD1d-mediated ?-GalCer presentation leads to rapid release of Th1 and Th2 cytokines. Since Th1 and Th2 cytokines antagonize each other’s effects, ?-GalCer analogues that induce a biased Th1/Th2 response are highly awaited. With the exception of a C-glycoside (?-C-GalCer), most of the known ?-GalCer analogues able to induce polarized cytokine responses are characterized by modifications of the phytosphingosine or fatty acyl chains, expected to alter the affinity for CD1d. Herein we describe the synthesis of 6?-modified ?-GalCer analogues with an intact phytoceramide moiety that are capable to skew the cytokine release profile to Th1, while maintaining strong antigenic activity. These analogues are characterized by the presence of an aromatic moiety that is connected via an amide or an urea linkage to C?-6 of the galactopyranose ring.
0002-7863
16468-16469
Trappeniers, Matthias
003338a8-2d89-453c-86ee-67c7464e1ac3
Van Beneden, Katrien
d8fc2c97-163b-4422-a513-34a08745a00c
Decruy, Tine
0d799625-7310-423a-b7a7-6ece86b8ea1a
Hillaert, Ulrik
84b7277c-4a71-45a8-95ea-ef60b3d3067b
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba
Elewaut, Dirk
98c0d9e0-e559-4f19-8a56-573fee3da83e
Van Calenbergh, Serge
9587a6e2-b48b-4f79-807d-b889c7a1d9d6
Trappeniers, Matthias
003338a8-2d89-453c-86ee-67c7464e1ac3
Van Beneden, Katrien
d8fc2c97-163b-4422-a513-34a08745a00c
Decruy, Tine
0d799625-7310-423a-b7a7-6ece86b8ea1a
Hillaert, Ulrik
84b7277c-4a71-45a8-95ea-ef60b3d3067b
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba
Elewaut, Dirk
98c0d9e0-e559-4f19-8a56-573fee3da83e
Van Calenbergh, Serge
9587a6e2-b48b-4f79-807d-b889c7a1d9d6

Trappeniers, Matthias, Van Beneden, Katrien, Decruy, Tine, Hillaert, Ulrik, Linclau, Bruno, Elewaut, Dirk and Van Calenbergh, Serge (2008) 6?-derivatised ?-galcer analogues capable of inducing strong CD1d-mediated Th1-biased NKT cell responses in mice. Journal of the American Chemical Society, 130 (49), 16468-16469. (doi:10.1021/ja8064182).

Record type: Article

Abstract

?-Galactosyl ceramide (?-GalCer, also known as KRN 7000) is known as the prototypical antigen for invariant natural killer T (NKT) cells. Stimulation of NKT cells by CD1d-mediated ?-GalCer presentation leads to rapid release of Th1 and Th2 cytokines. Since Th1 and Th2 cytokines antagonize each other’s effects, ?-GalCer analogues that induce a biased Th1/Th2 response are highly awaited. With the exception of a C-glycoside (?-C-GalCer), most of the known ?-GalCer analogues able to induce polarized cytokine responses are characterized by modifications of the phytosphingosine or fatty acyl chains, expected to alter the affinity for CD1d. Herein we describe the synthesis of 6?-modified ?-GalCer analogues with an intact phytoceramide moiety that are capable to skew the cytokine release profile to Th1, while maintaining strong antigenic activity. These analogues are characterized by the presence of an aromatic moiety that is connected via an amide or an urea linkage to C?-6 of the galactopyranose ring.

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More information

e-pub ahead of print date: 13 November 2008
Published date: 10 December 2008
Organisations: Chemistry

Identifiers

Local EPrints ID: 147921
URI: http://eprints.soton.ac.uk/id/eprint/147921
ISSN: 0002-7863
PURE UUID: 6a20ae5e-5d28-486d-998b-bc96fc9c997e
ORCID for Bruno Linclau: ORCID iD orcid.org/0000-0001-8762-0170

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Date deposited: 27 Apr 2010 08:28
Last modified: 19 Nov 2019 01:52

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Contributors

Author: Matthias Trappeniers
Author: Katrien Van Beneden
Author: Tine Decruy
Author: Ulrik Hillaert
Author: Bruno Linclau ORCID iD
Author: Dirk Elewaut
Author: Serge Van Calenbergh

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