Molecular basis of glycoalkaloid induced membrane disruption.
In this study the interaction between the glycoalkaloids alpha-chaconine, alpha-solanine and alpha-tomatine and sterols in model membranes was analysed systematically using techniques like membrane leakage, binding experiments, detergent extraction, electron microscopy, NMR and molecular modelling. The most important properties for sterols to interact with glycoalkaloids turned out to be a planer ring structure and a 3 beta-OH group, whereas for alpha-chaconine the 5-6 double bond and the 10-methyl group were also of importance. The importance of sugar-sugar interactions was illustrated by the high synergistic effect between alpha-chaconine and alpha-solanine, the leakage enhancing effect of glycolipids, and the almost complete loss of activity after deleting one or more mono-saccharides from the glycoalkaloids. The formed complexes which were resistant against detergent extraction existed of glycoalkaloid/sterol in a 1:1 ratio and formed tubular structures (alpha-chaconine) with an inner monolayer of phospholipids, whereas with alpha-tomatine also spherical structures were formed. Based on the results a molecular model for glycoalkaloid induced membrane disruption is presented.
Keukens
E A
EA
DLO Agrotechnological Research Institute (ATO-DLO), Wageningen, The Netherlands.
de Vrije
T
T
van den Boom
C
C
de Waard
P
P
Plasman
H H
HH
Thiel
F
F
Chupin
V
V
Jongen
W M
WM
de Kruijff
B
B
D002240:Carbohydrate Sequence; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D012992:Solanine / Q000031:analogs & derivatives* / Q000737:chemistry*; D013261:Sterols / Q000737:chemistry; D014053:Tomatine / Q000737:chemistry*
D008567:Membranes, Artificial; D013261:Sterols; D012992:Solanine; C011860:alpha-chaconine; D014053:Tomatine