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

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

  • Bioorg Med Chem Lett. 2025 Jun 1:121:130165. doi: 10.1016/j.bmcl.2025.130165.
Melanie A Franklin 1,  Mariam N Salib 2,  Juliette Gafni 3,  Isaac N Pessah 3,  Tadeusz F Molinski 4
Affiliations

Affiliations

  • 1 Department of Chemistry University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
  • 2 Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
  • 3 Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
  • 4 Department of Chemistry University of California, Davis, One Shields Avenue, Davis, CA 95616, USA; Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: [email protected].
PMID: 40043821 DOI: 10.1016/j.bmcl.2025.130165
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.

Keywords

Alkaloid; Ca(2+) channel; Marine natural product; Synthesis.

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