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

被引:25
作者
FUJIKAWA, A
IN, Y
INOUE, M
ISHIDA, T
NEMOTO, N
KOBAYASHI, Y
KATAOKA, R
IKAI, K
TAKESAKO, K
KATO, I
机构
[1] OSAKA UNIV PHARMACEUT SCI,DEPT PHYS CHEM,MATSUBARA,OSAKA 580,JAPAN
[2] OSAKA UNIV,INST PROT RES,SUITA,OSAKA 565,JAPAN
[3] RYOKA SYST INC,DEPT COMP SCI,URAYASU,CHIBA 279,JAPAN
[4] TAKARA SHUZO CO LTD,BIOTECHNOL RES LABS,OTSU,SHIGA 52021,JAPAN
关键词
D O I
10.1021/jo00082a013
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The solid-state and solution conformations of aureobasidin E, a new type of cyclic depsipeptide antibiotic, have been analyzed by X-ray diffraction and NMR spectroscopy to elucidate the possible relationship between 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) Angstrom, b = 10.638(3) Angstrom, c = 18.133(6) Angstrom,beta = 103.51(2)degrees, Z = 2] shows an arrowhead-like conformation of aureobasidin E stabilized by three transannular N-H...O=C hydrogen bonds, with the formation of three secondary structures of an antiparallel beta-sheet, and beta- and gamma-turns. The conformational analysis by means of NMR spectroscopy performed in DMSO solution and of simulated annealing calculations indicates that the solution structures are, on the whole, homologous to that observed in the solid state in such a way that the molecule forms an arrowhead-like conformation and the beta HOMeVal residue, which is indispensable for its bioactivity, is located at the same relative position. However, the omega torsion angle around the beta HOMePhe-Pro peptide bond (cis orientation in solution and trans orientation in solid state) and consequent intramolecular NH..O=C hydrogen bonding formation are different. This leads to the more flexible and rounded conformation of aureobasidin E in solution than in the solid state. The biological roles of some characteristic functional groups in the chemical structure of aureobasidin E are discussed on the basis of molecular conformation.
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页码:570 / 578
页数:9
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