Micropeptins from an Israeli Fishpond Water Bloom of the Cyanobacterium Microcystis sp.

Abstract

Seven new natural products, micropeptin MZ845 (1), micropeptin MZ859 (2), micropeptin MZ939A (3), micropeptin MZ925 (4), micropeptin MZ939B (5), micropeptin MZ1019 (6), and micropeptin MZ771 (7), as well as two known micropeptins, cyanopeptolin S (8) and cyanopeptolin SS (9), were isolated from the hydrophilic extract of the cyanobacterium Microcystis sp. that was collected from a fishpond in Kibbutz Ma'ayan Tzvi, Israel, in July 2006. The structures of the pure natural products were elucidated using spectroscopic methods, including UV, 1D and 2D NMR, and MS techniques. The absolute configuration of the chiral centers of the compounds was determined using Marfey's method for HPLC. The inhibitory activity of the compounds was determined for the serine proteases: trypsin, chymotrypsin, thrombin, and elastase. These micropeptins inhibited trypsin with IC(50)'s that varied between 0.6 and 24.2 microM. The SAR of these micropeptins is discussed.