Brevetoxin derivatives that inhibit toxin activity
Brevetoxin derivatives that inhibit toxin activity
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DOI：
10.1016/s1074-5521(00)00119-8
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发表时间：
2000-06-01
影响因子：
--
通讯作者：
Baden, DG
中科院分区：
文献类型：
--
作者：
Purkerson-Parker, SL;Fieber, LA;Baden, DG
Background: The brevetoxins are marine neurotoxins that interfere with the normal functions of the voltage-gated Na+ channel. We have identified two brevetoxin derivatives that do not exhibit pharmacological properties typical of the brevetoxins and that function as brevetoxin antagonists.Results: PbTx-3 and benzoyl-PbTx-3 elicited Na+ channel openings during steady-state depolarizations; however, two PbTx-3 derivatives retained their ability to bind to the receptor, but did not elicit Na+ channel openings. alpha-Naphthoyl-PbTx-3 acted as a PbTx-3 antagonist but did not affect Na+ channels that were not exposed to PbTx-3. beta-Naphthoyl-PbTx-3 reduced openings of Na+ channels that were not exposed to PbTx-3.Conclusions: Some modifications to the brevetoxin molecule do not alter either the binding properties or the activity of these toxins. Larger modifications to the K-ring sidechain do not interfere with binding but have profound effects on their pharmacological properties. This implies a critical function for the K-ring sidechain of the native toxin.
