Balansa, Walter, Islam, Robiul, Fontaine, Frank, Piggott, Andrew M., Zhang, Hua, Xiao, Xue, Webb, Timothy I., Gilbert, Daniel F., Lynch, Joseph W., and Capon, Robert J. (2013) Sesterterpene glycinyl-lactams: a new class of glycine receptor modulator from Australian marine sponges of the genus Psammocinia. Organic and Biomolecular Chemistry, 11. 4695. pp. 2695-4701.

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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.

Item ID:	65665
Item Type:	Article (Research - C1)
ISSN:	1477-0539
Copyright Information:	© The Royal Society of Chemistry
Date Deposited:	27 Jun 2024 01:10
FoR Codes:	03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030401 Biologically Active Molecules @ 40% 03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030499 Medicinal and Biomolecular Chemistry not elsewhere classified @ 20% 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060110 Receptors and Membrane Biology @ 40%
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