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.
Hermitamides A and B are lipopeptides isolated from a Papau n class="Chemical">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.
Authors: W I Li; F W Berman; T Okino; F Yokokawa; T Shioiri; W H Gerwick; T F Murray Journal: Proc Natl Acad Sci U S A Date: 2001-06-19 Impact factor: 11.205
Authors: R L Manger; L S Leja; S Y Lee; J M Hungerford; Y Hokama; R W Dickey; H R Granade; R Lewis; T Yasumoto; M M Wekell Journal: J AOAC Int Date: 1995 Mar-Apr Impact factor: 1.913
Authors: Robert N Hanson; Choon Young Lee; Carolyn J Friel; Robert Dilis; Alun Hughes; Eugene R DeSombre Journal: J Med Chem Date: 2003-07-03 Impact factor: 7.446
Authors: Daniel J Edwards; Brian L Marquez; Lisa M Nogle; Kerry McPhail; Douglas E Goeger; Mary Ann Roberts; William H Gerwick Journal: Chem Biol Date: 2004-06
Authors: Thomas H Walls; Scott C Grindrod; Dawn Beraud; Li Zhang; Aparna R Baheti; Sivanesan Dakshanamurthy; Manoj K Patel; Milton L Brown; Linda H MacArthur Journal: Bioorg Med Chem Date: 2012-07-03 Impact factor: 3.641