Lipid Bilayer Perturbation by the Snail Toxin 6-Bromo-2-Mercaptotryptamine Dimer does not Account for its Modulation of Voltage-Gated Potassium Channels

Autor:	Chris Dockendorff, Kenneth S. Eum, Stephen F. Martin, Radda Rusinova, Jon T. Sack, Ian H. Kimball, Helgi I. Ingólfsson, Richard W. Aldrich, Ruchi Kapoor, Thasin Peyear, Disha M. Gandhi, Olaf S. Andersen
Rok vydání:	2017
Předmět:	Indole test chemistry.chemical_compound Chemistry Stereochemistry Dimer Biophysics Ether Biological activity Voltage-gated potassium channel Lipid bilayer Potassium channel Ion channel
Zdroj:	Biophysical Journal. 112:246a-247a
ISSN:	0006-3495
DOI:	10.1016/j.bpj.2016.11.1348
Popis:	The marine snail toxin BrMT, a 6-bromo-2-mercaptotryptamine dimer, is a powerful, hydrophobic modulator of Kv1 and Kv4 voltage-gated potassium channels. It remains unclear how BrMT modulates these diverse channels, and given BrMT's hydrophobicity, whether it alters potassium channel function by perturbing lipid bilayer properties. We synthesized BrMT and 11 analogs to determine structure-activity relationships, and create more chemically stable ion channel modulators. We found the biological activity was retained when the labile disulfide bond between BrMT's indole groups was replaced with an ether or alkane linkage.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::8cbe9309bcb541b25520cb286511e6c4 https://doi.org/10.1016/j.bpj.2016.11.1348 Zobrazit plný text záznamu