Abstract
A novel class of macrolides for which the name sanglifehrins is proposed, has been discovered from actinomycete strains based on their high affinity binding for cyclophilin A (CypA), an immunophilin originally identified as a cytosolic protein binding cyclosporin A (CsA). The sanglifehrins were produced by Streptomyces sp. A92-308110. They were isolated and purified by extraction and several chromatographic, activity-guided steps. Sanglifehrins A and B exhibit a 10 to approximately 20 fold higher affinity for CypA than CsA, whereas the affinity of sanglifehrins C and D for CypA is comparable to that of CsA. Sanglifehrins exhibit a lower immunosuppressive activity than CsA when tested in the mixed lymphocyte reaction. Their in vitro activity indicates that they belong to a novel class of immunosuppressants.
MeSH terms
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Animals
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / isolation & purification
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Anti-Bacterial Agents / metabolism
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Anti-Bacterial Agents / pharmacology*
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Bone Marrow Cells / physiology
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Chromatography, High Pressure Liquid
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Chromatography, Thin Layer
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Cyclosporine / metabolism
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Immunophilins / metabolism
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Immunosuppressive Agents / chemistry
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Immunosuppressive Agents / isolation & purification
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Immunosuppressive Agents / metabolism
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Immunosuppressive Agents / pharmacology*
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Lactones / chemistry
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Lactones / isolation & purification
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Lactones / metabolism
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Lactones / pharmacology
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Lymphocyte Culture Test, Mixed
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Macrolides
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Mice
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Mice, Inbred BALB C
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Mice, Inbred CBA
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Spiro Compounds / chemistry
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Spiro Compounds / isolation & purification
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Spiro Compounds / metabolism
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Spiro Compounds / pharmacology
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Streptomyces / classification
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Streptomyces / growth & development
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Streptomyces / metabolism*
Substances
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Anti-Bacterial Agents
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Immunosuppressive Agents
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Lactones
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Macrolides
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Spiro Compounds
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sanglifehrin A
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sanglifehrin B
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sanglifehrin C
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sanglifehrin D
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Cyclosporine
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Immunophilins