TY - JOUR
T1 - Synthesis and evaluation of sphinganine analogues of KRN7000 and OCH
AU - Ndonye, Rachel M.
AU - Izmirian, Douglas P.
AU - Dunn, Matthew F.
AU - Yu, Karl O.A.
AU - Porcelli, Steven A.
AU - Khurana, Archana
AU - Kronenberg, Mitchell
AU - Richardson, Stewart K.
AU - Howell, Amy R.
PY - 2005/12/9
Y1 - 2005/12/9
N2 - The phytosphingosine-containing α-galactosylceramides (α-GalCers), KRN7000 and OCH, have been shown to activate NKT cells via interaction with CD1d, a member of the CD1 family of antigen presenting proteins. Evidence from KRN7000 stimulation of NKT cells suggests that α-GalCers may have applications in the treatment or prevention of a range of viral, bacterial, and autoimmune conditions. Moreover, OCH, a truncated analogue of KRN7000, appears to induce a TH2 bias, which could have implications for the treatment of autoimmune and inflammatory conditions. We have prepared the direct sphinganine-containing analogues of KRN7000 and OCH, 1 and 2, and found them to be comparable in activity to the parent compounds in inducing the release of IL-2, IL-4, and IFNγ. In addition, compound 2 leads to a cytokine bias similar to that seen with OCH. This is significant because sphinganines are more easily accessed than phytosphingosines, which should facilitate SAR studies.
AB - The phytosphingosine-containing α-galactosylceramides (α-GalCers), KRN7000 and OCH, have been shown to activate NKT cells via interaction with CD1d, a member of the CD1 family of antigen presenting proteins. Evidence from KRN7000 stimulation of NKT cells suggests that α-GalCers may have applications in the treatment or prevention of a range of viral, bacterial, and autoimmune conditions. Moreover, OCH, a truncated analogue of KRN7000, appears to induce a TH2 bias, which could have implications for the treatment of autoimmune and inflammatory conditions. We have prepared the direct sphinganine-containing analogues of KRN7000 and OCH, 1 and 2, and found them to be comparable in activity to the parent compounds in inducing the release of IL-2, IL-4, and IFNγ. In addition, compound 2 leads to a cytokine bias similar to that seen with OCH. This is significant because sphinganines are more easily accessed than phytosphingosines, which should facilitate SAR studies.
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U2 - 10.1021/jo051147h
DO - 10.1021/jo051147h
M3 - Article
C2 - 16323834
AN - SCOPUS:28744438007
SN - 0022-3263
VL - 70
SP - 10260
EP - 10270
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 25
ER -