Referenced in: none

Automatically associated channels: Nav1.2

Title: Synthesis and evaluation of hermitamides A and B as human voltage-gated sodium channel blockers.

Authors: Eliseu O De Oliveira, Kristin M Graf, Manoj K Patel, Aparna Baheti, Hye-Sik Kong, Linda H MacArthur, Sivanesan Dakshanamurthy, Kan Wang, Milton L Brown, Mikell Paige

Journal, date & volume: Bioorg. Med. Chem., 2011 Jul 15 , 19, 4322-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21683602

Abstract
Hermitamides A and B are lipopeptides isolated from a Papau New Guinea collection of the marine cyanobacterium Lyngbya majuscula. We hypothesized that the hermitamides are ligands for the human voltage-gated sodium channel (hNa(V)) based on their structural similarity to the jamaicamides. Herein, we describe the nonracemic total synthesis of hermitamides A and B and their epimers. We report the ability of the hermitamides to displace [(3)H]-BTX at 10 μM more potently than phenytoin, a clinically used sodium channel blocker. We also present a potential binding mode for (S)-hermitamide B in the BTX-binding site and electrophysiology showing that these compounds are potent blockers of the hNav1.2 voltage-gated sodium channel.