RCAI-133, an N-methylated analogue of KRN7000, activates mouse natural killer T cells to produce Th2-biased cytokines

Abstract

We synthesized seven new analogues of KRN7000: RCAI-133 and 154–159. RCAI-154, 156 and 158 are secondary-amide analogues having a hydroxy, a methyl or two methyl groups at the α-position of a linear C₁₈-acyl chain, respectively. RCAI-155, 157 and 159 are corresponding N-methylated tertiary amide analogues, and RCAI-133 is the N-methylated KRN7000. Among them, a PBS solution of RCAI-133 induced mouse lymphocytes to produce Th2-biasing cytokines in vivo, while RCAI-154–159 showed only weak or almost no immunostimulatory activity. Therefore, N-methylation led the glycolipid to produce predominantly Th2-type cytokines, while acyl α-substitution was detrimental to activity.