Abstract
31-O-Desmethylimmunomycin O: methyltransferase (DIMT), an enzyme involved in the biosynthesis of immunomycin (ascomycin/FR-900520), was used to synthesize three analogs of this immunosuppressant compound. These compounds were assigned the following structures: 13-O-desmethyl-, 15-O-desmethyl- and 13,15-O-bisdesmethyl-immunomycins. Two of these compounds, namely, 15-O-desmethyl- and 13,15-O-bismethyl-immunomycins have novel structures and were examined for possible immunosuppressive activity by in vitro T-cell proliferation assay. The results showed that methylation of the C-15 hydroxyl is critical for full biological activity of the immunomycin.
MeSH terms
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Animals
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Cell Division / drug effects
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Chromatography, High Pressure Liquid
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Chromatography, Thin Layer
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Enzymes / metabolism*
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Immunosuppressive Agents / chemistry
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Immunosuppressive Agents / metabolism*
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Immunosuppressive Agents / pharmacology
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Magnetic Resonance Spectroscopy
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Methylation
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Mice
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Mice, Inbred C57BL
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Spectrometry, Mass, Fast Atom Bombardment
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T-Lymphocytes / cytology
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T-Lymphocytes / drug effects
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Tacrolimus / analogs & derivatives*
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Tacrolimus / chemistry
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Tacrolimus / metabolism
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Tacrolimus / pharmacology
Substances
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Enzymes
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Immunosuppressive Agents
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15-O-desmethylascomycin
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13-O-desmethylascomycin
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13,15-O-bidesmethylascomycin
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Tacrolimus