ja200555a

Abstract Nove l immunosuppressants, ushikulides A and B, were isolated from the culture broth of Streptomyces sp. IUK-102. Ushikulides A and B both have the same molecular formula, determined as C 40 H 68 O 10 . The structures of both compounds were elucidated to be novel 22-membered macrolides. Both compounds showed immunosuppressive activity for murine splenocyte proliferation in vitro. Keywords 22-membered macrolides, ushikulide, immunosuppressants Cyclosporin A [1] and FK506 [2], extremely potent immunosuppressive agents, have revolutionized organ transplantation by blocking the activation of lymphocytes and are widely used in preventing rejection. Cyclosporin A and FK506 respectively bind to cyclophilin and FK506- binding protein (FKBP), so-called immunophilin [3]. Binding of each of these drug-protein complexes to a catalytic subunit of carcineurin causes inhibition of signal transduction in T cell activation [3]. However, these agents have some adverse side-effects such as nephrotoxicity and chronic rejection [4, 5]. Another potent immunosuppressiv e agent is desired to develop a safer medical treatment. During our screening for immunosuppressants from microbial products, novel immunosuppressants ushikulides A (1) and B (2) were found in the culture broth of Streptomyces sp. IUK-102 (Fig. 1). This paper describes the isolation, structure elucidation, and biological activities of these compounds. The producing strain, Streptomyces sp. IUK-102, was isolated from a soil sample collected in Ibaraki prefecture, J. An tibiot. 58(6): 420– 424, 2005 NOTE Ushikulides A and B, Immunosuppre ssants Produced by a Strain of Streptomyces sp. Kosaku Takahashi, Teruhiko Y oshihara, Kazuhiko Kurosawa Received: April 27, 2005 / Accepted: June 1, 2005 © Japan Antibiotics Resea rch Association THE JOURNAL OF ANTIBIOTICS K. Takahashi (Corresponding author) , T. Yoshihara: Graduate School of Agriculture, Hokkaido University, Sapporo, 060-8589, Japan, E-mail: [email protected] K. Kurosawa: Department of Biology 68-370, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge MA 02139, USA Fi g. 1 Structures of ushikulides A ( 1) and B (2).

Documents

ja200555a