Differences in ion-channel formation by ampullosporins B, C, D and semisynthetic desacetyltryptophanyl ampullosporin A.
Peptaibol-type ampullosporins B (2) and D (4) are capable of forming ion-conducting pores in planar lipid bilayer membrane prepared from soybean phosphatidylcholine in a similar manner as it was shown for ampullosporin A (1). However, the isomeric ampullosporin C (3) was required in 20-fold higher concentration to afford a comparable effect. In contrast to 1, 2, 3 and 4, the desacetyltryptophanyl ampullosporin A (5) failed to form ion channels. The results suggest that the sequence of amino acids especially at positions 8-10, the nitrogen-terminal acetyl residues and tryptophane are major factors determining ion-channel formation within bilayer membranes. The differences in membrane activities were comparable to the observed biological activities.
Grigoriev
P A
PA
Institute of Cell Biophysics, Russian Academy of Sciences, RU-142292 Pushchino, Moscow Region, Russia.
Kronen
M
M
Schlegel
B
B
Härtl
A
A
Gräfe
U
U
D000900:Anti-Bacterial Agents / Q000145:classification / Q000378:metabolism* / Q000494:pharmacology; D004553:Electric Conductivity; D007473:Ion Channels / Q000096:biosynthesis* / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D008564:Membrane Potentials; D008567:Membranes, Artificial; D054848:Peptaibols; D010455:Peptides; D010713:Phosphatidylcholines / Q000378:metabolism*; D013025:Glycine max / Q000378:metabolism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007473:Ion Channels; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D054848:Peptaibols; D010455:Peptides; D010713:Phosphatidylcholines; C109004:ampullosporin