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Issue 28, 2013
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Sesterterpene glycinyl-lactams: a new class of glycine receptor modulator from Australian marine sponges of the genus Psammocinia

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Abstract

Bioassay guided fractionation of three southern Australian marine sponges of the genus Psammocinia, selected for their ability to modulate glycine-gated chloride channel receptors (GlyRs), yielded the rare marine sesterterpenes (−)-ircinianin (1) and (−)-ircinianin sulfate (2), along with the new biosynthetically related metabolites (−)-ircinianin lactam A (3), (−)-ircinianin lactam A sulfate (4), (−)-oxoircinianin (5), (−)-oxoircinianin lactam A (6) and (−)-ircinianin lactone A (7). Acetylation of 1 returned (−)-ircinianin acetate (8). Whole cell patch-clamp electrophysiology on 1–8 established 3 as an exceptionally potent and selective α3 GlyR potentiator, and 6 as a selective α1 GlyR potentiator. The discovery and characterization of sesterterpenes 1–8, and in particular the glycinyl-lactams 3 and 6, provide valuable new insights into GlyR pharmacology. These insights have the potential to inform and inspire the development of new molecular tools to probe GlyR distribution and function, and therapeutics to treat a wide array of GlyR mediated diseases and disorders.

Graphical abstract: Sesterterpene glycinyl-lactams: a new class of glycine receptor modulator from Australian marine sponges of the genus Psammocinia

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Publication details

The article was received on 26 Apr 2013, accepted on 23 May 2013 and first published on 30 May 2013


Article type: Paper
DOI: 10.1039/C3OB40861B
Citation: Org. Biomol. Chem., 2013,11, 4695-4701
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    Sesterterpene glycinyl-lactams: a new class of glycine receptor modulator from Australian marine sponges of the genus Psammocinia

    W. Balansa, R. Islam, F. Fontaine, A. M. Piggott, H. Zhang, X. Xiao, T. I. Webb, D. F. Gilbert, J. W. Lynch and R. J. Capon, Org. Biomol. Chem., 2013, 11, 4695
    DOI: 10.1039/C3OB40861B

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