Solution NMR structures of the polyene macrolide antibiotic filipin III

The solution structure of filipin III, an antifungal polyene macrolide bios ynthesized by Streptomyces filipinensis and widely used for the detection a nd the quantitation of cholesterol ill biomembranes, has been calculated wi th a set of geometrical restraints derived from H-1 NMR in DMSO-d(6) at 25 degrees C, Filipin III appears as a rod-shaped molecule of 18 Angstrom leng th. Its amphiphilic structure is made of an all-syn 1,3-polyol motif, stabi lized by intramolecular hydrogen bonds on one side, and a conjugated pentae ne moiety on the other side of the molecule, The overall shape is comparabl e to cholesterol, and the molecular structure of filipin III affords a firs t molecular basis to the comprehensive understanding of the interactions po ssible in the filipin III-cholesterol complex which is still unknown at the atomic resolution. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.