Matthias Trappeniers

Publications of Matthias Trappeniers

• Galactose-modified iNKT cell agonists stabilized by an induced fit of CD1d prevent tumour metastasis.

  Authors: Sandrine Aspeslagh, Yali Li, Esther Dawen Yu, Nora Pauwels, Matthias Trappeniers, Enrico Girardi, Tine Decruy, Katrien Van Beneden, Koen Venken, Michael Drennan, Luc Leybaert, Jing Wang, Richard W Franck, Serge Van Calenbergh, Dirk M Zajonc, Dirk Elewaut

  The EMBO journal. 06/2011; 30(11):2294-305.

  Invariant natural killer T (iNKT) cells are known to have marked immunomodulatory capacity due to their ability to produce copious amounts of effector cytokines. Here, we report the structure andInvariant natural killer T (iNKT) cells are known to have marked immunomodulatory capacity due to their ability to produce copious amounts of effector cytokines. Here, we report the structure and function of a novel class of aromatic α-galactosylceramide structurally related glycolipids with marked Th1 bias in both mice and men, leading to superior tumour protection in vivo. The strength of the Th1 response correlates well with enhanced lipid binding to CD1d as a result of an induced fit mechanism that binds the aromatic substitution as a third anchor, in addition to the two lipid chains. This induced fit is in contrast to another Th1-biasing glycolipid, α-C-GalCer, whose CD1d binding follows a conventional key-lock principle. These findings highlight the previously unexploited flexibility of CD1d in accommodating galactose-modified glycolipids and broaden the range of glycolipids that can stimulate iNKT cells. We speculate that glycolipids can be designed that induce a similar fit, thereby leading to superior and more sustained iNKT cell responses in vivo.

• Synthesis and evaluation of amino-modified alpha-GalCer analogues.

  Authors: Matthias Trappeniers, René Chofor, Sandrine Aspeslagh, Yali Li, Bruno Linclau, Dirk M Zajonc, Dirk Elewaut, Serge Van Calenbergh

  Organic letters. 07/2010; 12(13):2928-31.

  Alpha-GalCer analogues featuring a phytoceramide 3- and 4-amino group have been synthesized. A Mitsunobu reaction involving phthalimide was employed for the introduction of the amino groups at the 3-Alpha-GalCer analogues featuring a phytoceramide 3- and 4-amino group have been synthesized. A Mitsunobu reaction involving phthalimide was employed for the introduction of the amino groups at the 3- and 4-positions of suitable phytosphingosine-derived precursors. The influence of these modifications on the interaction with the T-cell receptor of NKT cells was investigated, as well as the capacity of the amino-modified analogues to induce a cytokine response after in vivo administration.

• The Synthesis and in vivo Evaluation of 2',2'-Difluoro KRN7000.

  Authors: Leo Leung, Cyrille Tomassi, Katrien Van Beneden, Tine Decruy, Matthias Trappeniers, Dirk Elewaut, Yifang Gao, Tim Elliott, Aymen Al-Shamkhani, Christian Ottensmeier, Jörn M Werner, Anthony Williams, Serge Van Calenbergh, Bruno Linclau

  ChemMedChem. 02/2009;

• 6'-derivatised alpha-GalCer analogues capable of inducing strong CD1d-mediated Th1-biased NKT cell responses in mice.

  Authors: Matthias Trappeniers, Katrien Van Beneden, Tine Decruy, Ulrik Hillaert, Bruno Linclau, Dirk Elewaut, Serge Van Calenbergh

  Journal of the American Chemical Society. 01/2009; 130(49):16468-9.

• Synthesis and in vitro evaluation of alpha-GalCer epimers.

  Authors: Matthias Trappeniers, Stijn Goormans, Katrien Van Beneden, Tine Decruy, Bruno Linclau, Aymen Al-Shamkhani, Tim Elliott, Christian Ottensmeier, Joern M Werner, Dirk Elewaut, Serge Van Calenbergh

  ChemMedChem. 08/2008; 3(7):1061-70.

  alpha-GalCer (also known as KRN7000) is an immunomodulatory glycolipid that is known to potently activate invariant natural killer T (NKT) cells upon CD1d-mediated stimulation. Because Th1 and Th2alpha-GalCer (also known as KRN7000) is an immunomodulatory glycolipid that is known to potently activate invariant natural killer T (NKT) cells upon CD1d-mediated stimulation. Because Th1 and Th2 cytokines, which are released after alpha-GalCer presentation, antagonize each other's effects, alpha-GalCer analogues that induce a biased Th1/Th2 response are highly awaited. In this context, we report the synthesis and in vitro evaluation of alpha-Gal-D-xylo-Cer and two alpha-Gal-L-lyxo-Cer analogues, one with the natural acyl chain, the other with a truncated chain.