Autumnalamide, a Prenylated Cyclic Peptide from the Cyanobacterium Phormidium autumnale, Acts on SH-SY5Y Cells at the Mitochondrial Level

• Published in: Journal of natural products (Washington, D.C.) Vol. 77; no. 10; pp. 2196 - 2205
• Main Authors: Audoin, Coralie, Sánchez, Jon Andoni, Genta-Jouve, Grégory, Alfonso, Amparo, Rios, Laurent, Vale, Carmen, Thomas, Olivier P, Botana, Luis M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 24-10-2014
• Subjects: Cyanobacteria; Cyanobacteria - chemistry; Humans; Molecular Structure; Peptides, Cyclic - chemistry; Peptides, Cyclic - isolation & purification; Peptides, Cyclic - pharmacology; Phormidium; Phormidium autumnale; Thapsigargin - pharmacology
• DOI: 10.1021/np500374a
• EISSN: 1520-6025
• ISSN: 0163-3864

Filamentous cyanobacteria of the genus Phormidium have been rarely studied for their chemical diversity. For the first time, the cultivable Phormidium autumnale was shown to produce a prenylated cyclic peptide named autumnalamide (1). The structure of this peptide was fully determined after a deep exploration of the spectroscopic data, including NMR and HRMS. Interestingly, a prenyl moiety was located on the guanidine end of the arginine amino acid. The absolute configurations of most amino acids were assessed using enantioselective GC/MS analysis, with 13C NMR modeling being used for the determination of d-arginine and d-proline. The effects of 1 on sodium and calcium fluxes were studied in SH-SY5Y and hNav 1.6 HEK cells. When the Ca2+ influx was stimulated by thapsigargin, strong inhibition was observed in the presence of 1. As a consequence, this compound may act by disrupting the normal calcium uptake of this organelle, inducing the opening of the mitochondrial permeability transition pore, which results in the indirect blockade of store-operated channels.