RT Journal Article
SR Electronic
T1 Conformations of fortimicins and three-dimensional structure-activity relationship in the aminoglycoside antibiotics.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 127
OP 132
VO 23
IS 1
A1 N Hirayama
A1 K Shirahata
A1 Y Ohashi
A1 Y Sasada
YR 1983
UL http://molpharm.aspetjournals.org/content/23/1/127.abstract
AB The fortimicins are pseudodisaccharide antibiotics consisting of purpurosamine and fortamine moieties which are connected through an alpha-linkage. NMR spectra indicate that the fortamine ring in fortimicin A takes a chair conformation which corresponds to an inverted one in the conformation of fortimicin B free base. Fortimicin A is unstable in solution, and we were unable to obtain any crystals of it. To elucidate the structure of fortimicin A and to clarify the stereochemistry of fortimicins, we have undertaken to calculate their empirical force-fields starting from the X-ray structures of fortamines and fortimicin B free base. Nuclear Overhauser enhancement data were also employed to confirm the calculated relative orientation of the two rings around the glycosidic linkage. The 3-dimensional structure-activity relationship of aminoglycoside antibiotics is discussed on the basis of these results.