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Synthesis and Evaluation of Sphingolipid Analogues
Author(s) -
Mathew Thresen,
Billich Andreas,
Cavallari Marco,
Bornancin Frederic,
Nussbaumer Peter,
De Libero Gennaro,
Vasella Andrea
Publication year - 2009
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200900013
Subject(s) - ceramide , cd1d , chemistry , sphingomyelin , sphingolipid , stereochemistry , azide , transfection , click chemistry , biochemistry , natural killer t cell , combinatorial chemistry , in vitro , membrane , gene , apoptosis , organic chemistry , cytotoxic t cell
The analogues 7 – 9 of 7‐oxaceramide and 7‐oxasphingosine were synthesized from the known azidosphingosine 21 . The 1,4‐disubstituted 1,2,3‐triazole analogues 10 – 16 of ceramides were synthesized by the click reaction of the known azide 24 . None of the analogues 7 – 15 was active as inhibitor of SPHK type 1 and of acid sphingomyelinase, whereas 16 is a weak inhibitor of SPHK1. Triazoles 10, 11 , and 15 did not inhibit ceramide phosphorylation by CerK, and none of 7, 8 , and 10 – 15 activated invariant natural killer T (iNKT) cell clones when presented by human CD1d‐transfected antigen‐presenting cells (APC) or by plate‐bound human CD1d [55]. Triazoles 14 and 15 prevent binding of α ‐galactosylceramide ( α ‐GalCer) to plate‐bound human CD1d and subsequent T‐cell response to α ‐GalCer. Only 15 reduced activation by α ‐GalCer significantly and independently of the cytokine measured.