TY - JOUR T1 - Conformations of fortimicins and three-dimensional structure-activity relationship in the aminoglycoside antibiotics. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 127 LP - 132 VL - 23 IS - 1 AU - N Hirayama AU - K Shirahata AU - Y Ohashi AU - Y Sasada Y1 - 1983/01/01 UR - http://molpharm.aspetjournals.org/content/23/1/127.abstract N2 - 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. ER -