RCAI-37, 56, 59, 60, 92, 101, and 102, cyclitol and carbasugar analogs of KRN7000: their synthesis and bioactivity for mouse lymphocytes to produce Th1-biased cytokines.
Cyclitol [RCAI-37 (1), 59 (5), 92 (7), and 102 (2)] and carbasugar analogs [RCAI-56 (3), 60 (4), and 101 (6)] of KRN7000 were synthesized through coupling reactions of the corresponding cyclitol or carbasugar derivatives with a cyclic sulfamidate (9) as the key step. Bioassay showed RCAI-56 (3, carbagalactose analog of KRN7000), 59 (5, 1-deoxy-neo-inositol analog), and 92 (7, 1-O-methylated 5) to be remarkably potent stimulants of mouse lymphocytes to produce Th1-biased cytokines, such as interferon-gamma, in vivo. RCAI-60 (4, carbafucose analog) and RCAI-101 (6, 6-O-methylated 3) showed strong bioactivity, on the other hands, RCAI-37 (1, myo-inositol analog) and 102 (2, neo-inositol analog) induced little cytokine production.
Tashiro
Takuya
T
Glycosphingolipid Synthesis Group, Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan.
Nakagawa
Ryusuke
R
Hirokawa
Takatsugu
T
Inoue
Sayo
S
Watarai
Hiroshi
H
Taniguchi
Masaru
M
Mori
Kenji
K
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D054329:Carbasugars / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054812:Cyclitols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D005699:Galactosylceramides / Q000737:chemistry*; D007371:Interferon-gamma / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D054329:Carbasugars; D054812:Cyclitols; D016207:Cytokines; D005699:Galactosylceramides; D007371:Interferon-gamma; C103873:KRN 7000