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.
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.
Authors: Sophie Michelliza; William M Abraham; Henry M Jacocks; Thomas Schuster; Daniel G Baden Journal: Chembiochem Date: 2007-12-17 Impact factor: 3.164
Authors: Barbara Kirkpatrick; Lora E Fleming; Dominick Squicciarini; Lorrie C Backer; Richard Clark; William Abraham; Janet Benson; Yung Sung Cheng; David Johnson; Richard Pierce; Julia Zaias; Gregory D Bossart; Daniel G Baden Journal: Harmful Algae Date: 2004-04-01 Impact factor: 4.273
Authors: William M Abraham; Andrea J Bourdelais; Juan R Sabater; Ashfaq Ahmed; Troy A Lee; Irakli Serebriakov; Daniel G Baden Journal: Am J Respir Crit Care Med Date: 2004-09-24 Impact factor: 21.405
Authors: Andrea J Bourdelais; Susan Campbell; Henry Jacocks; Jerome Naar; Jeffery L C Wright; Jigani Carsi; Daniel G Baden Journal: Cell Mol Neurobiol Date: 2004-08 Impact factor: 5.046