Simplified cyclic analogues of bastadin-5. Structure-activity relationships for modulation of the RyR1/FKBP12 Ca2+ channel complex.

ABSTRACT: Bastadin-5, a brominated macro-dilactam from the marine sponge Ianthella basta, enhances release of Ca2+ from stores within the sarcoplasmic reticulum (SR) of muscle and nonmuscle cells by modulating RyR1/FKBP12 complex. Analogues of bastadin-5 present desirable targets for SAR studies to shed light on the gating mechanism and locus of bastadin-5 binding on these heteromeric channels that mediate essential steps in early coupling of membrane excitation to Ca2+ signaling cascades. Simple, ring-constrained analogues of bastadin-5 were synthesized from substituted benzaldehydes in a convergent manner, featuring an efficient S(N)Ar macroetherification, and evaluated in an assay that measures [3H]-ryanodine that is known to correlate with the functional open state of the Ca2+ channel. The simpl

SUBMITTER: Masuno MN 

PROVIDER: S-EPMC3987770 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature