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Phosphorylation by Sphingosine Kinase 2 is Essential for in vivo Potency of FTY720 Analogues
Author(s) -
Högenauer Klemens,
Billich Andreas,
Pally Charles,
Streiff Markus,
Wagner Trixie,
Welzenbach Karl,
Nussbaumer Peter
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800037
Subject(s) - sphingosine , diastereomer , phosphorylation , in vivo , kinase , chemistry , potency , sphingosine kinase , epimer , sphingosine kinase 1 , in vitro , biochemistry , stereochemistry , sphingosine 1 phosphate , pharmacology , biology , genetics , receptor
Decisive diastereomers. Sphingosine kinase 2 (SPHK2) phosphorylation rate was found to be the major limiting factor for decreasing peripheral lymphocyte counts of FTY720‐like derivatives in vivo. For a diastereomeric pair of potent S1P1 agonists, lymphopenia was only observed for the epimer showing an efficient SPHK2 phosphorylation rate of the parent amino alcohol.