Abstract
We synthesized ten new analogs of 6'-modified KRN7000 (A): RCAI-58, 61, 64, 83, 85-87, 113, 119, and 125. They could be synthesized by α-selective galactosylation of ceramide 9 with the 6-modified D-galactopyranosyl fluorides (8a-8f) or L-arabinopyranosyl fluoride (17), or by etherification of the known alcohol 19. Bioassay of the ten analogs demonstrated that RCAI-61 (1, 6'-O-methylated analog of A) was the most potent immunostimulant among them, and could induce the production of a large amount of IFN-γ even at a low concentration in mice in vivo.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / chemical synthesis*
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Adjuvants, Immunologic / pharmacology
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Biological Assay
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Galactosylceramides / chemical synthesis*
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Galactosylceramides / pharmacology
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Interferon-gamma / agonists*
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Interferon-gamma / biosynthesis
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Interferon-gamma / immunology
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Interleukin-12 / agonists
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Interleukin-12 / biosynthesis
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Interleukin-12 / immunology
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Interleukin-4 / antagonists & inhibitors
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Interleukin-4 / biosynthesis
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Interleukin-4 / immunology
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Killer Cells, Natural / cytology
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Killer Cells, Natural / drug effects*
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Killer Cells, Natural / immunology
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Mice
Substances
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Adjuvants, Immunologic
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Antineoplastic Agents
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Galactosylceramides
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Interleukin-12
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Interleukin-4
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Interferon-gamma
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KRN 7000