Synthesis and biological activity of ester and ether analogues of alpha-galactosylceramide (KRN7000).
Alpha-Galactosylceramide (alphaGalCer, KRN7000) has been identified as a modulator of immunological processes through its capacity to bind iNKT cells mediated by CD1d molecules. Some analogues in while the amide group in alphaGalCer is replaced with ester or ether groups were synthesized from d-arabinitol or l-ribose to evaluate their ability to activate iNKT cells. Ester analogues 30a, 31a, and 61 showed activity for IFNgamma and IL-4 production of iNKT cells, while ether (31b) and 4-methoxy ester (76) analogues of alpha-galactosylceramide were not active for iNKT cells.
Shiozaki
Masao
M
Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan. shiozaki@rcai.riken.jp
Tashiro
Takuya
T
Koshino
Hiroyuki
H
Nakagawa
Ryusuke
R
Inoue
Sayo
S
Shigeura
Tomokuni
T
Watarai
Hiroshi
H
Taniguchi
Masaru
M
Mori
Kenji
K
D000818:Animals; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005699:Galactosylceramides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood; D051379:Mice; D008968:Molecular Conformation; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology; D013237:Stereoisomerism
D004952:Esters; D004987:Ethers; D005699:Galactosylceramides; D015847:Interleukin-4; D007371:Interferon-gamma; C103873:KRN 7000