TAILIEUCHUNG - Báo cáo khoa học: Solution NMR structure of five representative glycosylated polyene macrolide antibiotics with a sterol-dependent antifungal activity

Glycosylatedpolyenemacrolide antibiotics, as nystatins and amphotericins, are amphiphilic structures known to exert antifungal activity by disrupting the fungal cell membrane, leading to leakage of cellular materials, and cell death. This membrane disruption is strongly influenced by the presence and the exact nature of the membrane sterols. The solution structures of five representative glycosylatedmembers, three tetraenes (pimaricin, nystatin A1and rimocidin) and two heptaenes (candidin and vacidin A) have been calculated using geometric restraints derived from 1 H-NMR data and random searches of their conformational space | Eur. J. Biochem. 269 4533-4541 2002 FEBS 2002 doi Solution NMR structure of five representative glycosylated polyene macrolide antibiotics with a sterol-dependent antifungal activity Laurent Volpon and Jean-Marc Lancelin Laboratoire de RMN Biomoleculaire associe au CNRS Universite Claude Bernard - Lyon 1 and Ecole Superieure de Chimie Physique Electronique de Lyon Villeurbanne France Glycosylated polyene macrolide antibiotics as nystatins and amphotericins are amphiphilic structures known to exert antifungal activity by disrupting the fungal cell membrane leading to leakage of cellular materials and cell death. This membrane disruption is strongly influenced by the presence and the exact nature of the membrane sterols. The solution structures of five representative glycosylated members three tetraenes pimaricin nystatin A1 add ridiocidin add two heptaenes candidin and vacidin An have been calculated using geometric restraints derived from 1H-NMR data and random searches of their conformational space. Despite a different apparent structural order the NMR solutions structure indicate that the hydroxyl groups all clustered on one side of the rod-shaped structures and the glycosyl moieties are structurally conserved both in their conformation and their apparent order. The molecular structures afford an understanding of their selective interaction with the membrane sterols and the design of new polyene macrolides with improved activities. Keywords antifungal antibiotics polyene macrolides steroldependant antibiotics NMR solution structure 1 3-polyols. The vast family of polyenes antibiotics 1 2 includes amphiphilic compounds mostly produced by Streptomyces species with potent antifungal properties. Polyene macrolides are of an authentic clinical value for efficient therapies against animals and human infectious diseases caused by pathogenic fungi. In particular nystatin A1 amphotericin B and pimaricin natamycin are the most common .

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