Sanglifehrins A, B, C and D, novel cyclophilin-binding compounds isolated from Streptomyces sp A92-308110 - I. Taxonomy, fermentation, isolation and biological activity

A novel class of macrolides for which the name sanglifehrins is proposed, h as been discovered from actinomycete strains based on their high affinity b inding for cyclophilin A (CypA), an immunophilin originally identified as a cytosolic protein binding cyclosporin A (CsA). The sanglifehrins were prod uced by Streptomyces sp. A92-308110. They were isolated and purified by ext raction and several chromatographic, activity-guided steps. Sanglifehrins A and B exhibit a 10 similar to 20 fold higher affinity for CypA than CsA, w hereas 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 indic ates that they belong to a novel class of immunosuppressants.