Structure-activity of Bastadins from the marine sponge Ianthella basta. Modulators of the RYR1 Ca2+ channel

Abstract

The RYR1 Ca²⁺ channel mediates essential steps of excitation-contraction in skeletal muscle. Bastadins-5 and -6, highly brominated macrodilactams assembled from tyrosine and tyramine by the marine sponge Ianthella basta, were identified as potent sensitizers of RYR1 channel activation. Here, we present a structure-activity relationships study of a wide panel of bastadins, and related analogs, and define the minimum requirements for stabilizing the RYR1 complex open or closed conformations.