Premium
Synthesis of 7‐Aza‐ and 7‐Thiasphingosines, and Evaluation of Their Interaction with Sphingosine Kinases and with T‐Cells
Author(s) -
Mathew Thresen,
Billaud Célia,
Billich Andreas,
Cavallari Marco,
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.200900039
Subject(s) - sphingosine , cd1d , chemistry , sphingolipid , sphingosine kinase , kinase , transfection , recombinant dna , biochemistry , microbiology and biotechnology , sphingosine 1 phosphate , stereochemistry , in vitro , receptor , natural killer t cell , biology , gene , cytotoxic t cell
The synthesis of 7‐oxasphingosine ( 3 ) and 7‐oxaceramide ( 4 ) was improved by starting from the 4‐methoxybenzyl‐protected d‐ galactal 9 . The sphingosine analogues 5 – 7 and 24 were synthesized via the azido alcohol 13 . The 7‐thiasphingosine 5 is a poorer substrate for both isoforms of sphingosine kinase (SPHK) than sphingosine, but showed a slight preference for SPHK2. The sulfone 6 and the 7‐aza compounds 7 and 24 were not phosphorylated by either SPHK1 or SPHK2, and none of 5 – 7 and 24 activated invariant natural killer T (iNKT) cell clones when presented by human CD1d‐transfected antigen‐presenting cells (APC) or by plate‐bound human CD1d. Only 7 and 24 associated with plate‐bound recombinant CD1d prevented stimulation of iNKT cells by α ‐galactosylceramide ( α ‐GalCer).