X-RAY AND NMR CONFORMATIONAL STUDY OF AUREOBASIDIN-E - A CYCLIC DEPSIPEPTIDE WITH POTENT ANTIFUNGAL ACTIVITY

The solid-state and solution conformations of aureobasidin E, a new ty pe of cyclic depsipeptide antibiotic, have been analyzed by X-ray diff raction and NMR spectroscopy to elucidate the possible relationship be tween its molecular conformation and antifungal bioactivity. The X-ray analysis of the crystal structure recrystallized from hexane-propan-2 -ol-acetonitrile [monoclinic, space group P2(1), a = 16.458(3) Angstro m, b = 10.638(3) Angstrom, c = 18.133(6) Angstrom,beta = 103.51(2)degr ees, Z = 2] shows an arrowhead-like conformation of aureobasidin E sta bilized by three transannular N-H...O=C hydrogen bonds, with the forma tion of three secondary structures of an antiparallel beta-sheet, and beta- and gamma-turns. The conformational analysis by means of NMR spe ctroscopy performed in DMSO solution and of simulated annealing calcul ations indicates that the solution structures are, on the whole, homol ogous to that observed in the solid state in such a way that the molec ule forms an arrowhead-like conformation and the beta HOMeVal residue, which is indispensable for its bioactivity, is located at the same re lative position. However, the omega torsion angle around the beta HOMe Phe-Pro peptide bond (cis orientation in solution and trans orientatio n in solid state) and consequent intramolecular NH..O=C hydrogen bondi ng formation are different. This leads to the more flexible and rounde d conformation of aureobasidin E in solution than in the solid state. The biological roles of some characteristic functional groups in the c hemical structure of aureobasidin E are discussed on the basis of mole cular conformation.