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Total Enantioselective Synthesis and In Vivo Biological Evaluation of a Novel Fluorescent BODIPY α ‐Galactosylceramide
Author(s) -
VoHoang Yen,
Micouin Laurent,
Ronet Catherine,
Gachelin Gabriel,
Bonin Martine
Publication year - 2003
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200390009
Subject(s) - enantioselective synthesis , bodipy , fluorescence , in vivo , chemistry , combinatorial chemistry , biochemistry , stereochemistry , biology , catalysis , microbiology and biotechnology , physics , quantum mechanics
Abstract Natural killer T (NKT) cells are a distinct subset of mature lymphocytes endowed with features of activated and regulatory T cells. α ‐Galactosylceramides ( α ‐GalCers), the synthetic prototype of which is KRN7000, are the only natural reagents recognised by the T‐cell receptor of NKT cells. The α‐GalCer‐activated NKT cells promptly release IFN γ and IL‐4 (IFN=interferon; IL=interleukin) and undergo apoptotic death within hours. In mice, activated NKT cells are responsible for antitumour activity and protection against autoimmune diseases. KRN7000 can thus be considered as the root of a family of novel immunoregulatory drugs. To get insights into the in vivo behaviour of α‐galactosylceramides, an original fluorescent derivative has been prepared by following a convergent synthetic scheme. This strategy allows the introduction of different acyl chains, carbohydrate residues and various labels in the final steps of the synthesis. The fluorescent BODIPY probe derived from a versatile glycolipid precursor is as active as KRN7000 for inducing apoptosis of liver NKT cells. Fluorescence was detected in peritoneal macrophages and splenic antigen‐presenting cells, in Kupffer‐like cells in the liver, but not in lymphocytes.