Symplocin A, a Linear Peptide from the Bahamian Cyanobacterium <i>Symploca</i> sp. Configurational Analysis of <i>N</i>,<i>N</i>-Dimethylamino Acids by Chiral-Phase HPLC of Naphthacyl Esters

Abstract

The absolute stereostructures of the components of symplocin A (<b>3</b>), a new <i>N</i>,<i>N</i>-dimethyl-terminated peptide from the Bahamian cyanobacterium <i>Symploca</i> sp., were assigned from spectroscopic analysis, including MS, 2D NMR, and Marfey’s analysis. The complete absolute configuration of symplocin A, including the unexpected d-configurations of the terminal <i>N</i>,<i>N</i>-dimethylisoleucine and valic acid residues, was assigned by chiral-phase HPLC of the corresponding 2-naphthacyl esters, a highly sensitive, complementary strategy for assignment of N-blocked peptide residues where Marfey’s method is ineffectual or other methods fall short. Symplocin A exhibited potent activity as an inhibitor of cathepsin E (IC₅₀ 300 pM)