Actions of epimers of 12-(OH)-reduced saxitoxin and of 11-(OSO3)-saxitoxin on squid axon.
The actions of the 12 alpha-saxitoxinol, 12 beta-saxitoxinol and a C-12 ethylene thioketal derivative of saxitoxin, as well as those of 11 alpha-(OSO3)-saxitoxin, 11 beta-(OSO3)-saxitoxin and 11 alpha-(OH)-saxitoxin, have been examined on the isolated squid giant axon. Each of these analogues acted similarly to saxitoxin in blocking specifically the sodium channel. The relative potencies are: STX (1); 11 beta-(OSO3)-STX (gonyautoxin III) (0.42); 11 alpha-(OSO3)-STX (gonyautoxin II) (0.20); 11 alpha-(OH)-STX (0.10); 12 alpha-saxitoxinol (0.0021); 12 beta-saxitoxinol (0.0005). Thus, the presence of a bulky and negatively charged sulphate group on C-11 does not materially affect the biological activity of STX. Hydrogen bonding at the C-12 position is probably an important means of binding of STX to the membrane receptor site. The difference between the epimers of saxitoxinol suggests that the H in one of them may be geometrically better aligned than that in the other, with the hydrogen acceptor group in the receptor.
C Y
CY
Kao
P N
PN
Kao
M R
MR
James-Kracke
F E
FE
Koehn
C F
CF
Wichmann
H K
HK
Schnoes
D029845:Amphibian Proteins; D000818:Animals; D001369:Axons / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism; D049832:Decapodiformes; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D012530:Saxitoxin / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D012964:Sodium / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D029845:Amphibian Proteins; D002352:Carrier Proteins; D007473:Ion Channels; C027525:saxitoxin-binding protein, Rana catesbeiana; D012530:Saxitoxin; D012964:Sodium