Protease inhibitors from a water bloom of the cyanobacterium Microcystis aeruginosa.
Bioassay-guided fractionation of the polar extract of a Microcystis aeruginosa water bloom biomass yielded 10 micropeptins and one anabaenopeptin. Eight of the micropeptins, micropeptins HU1069 (1), HU989 (2), HU1021 (3), HU1041 (4), HU975 (5), HU895A (6), HU909 (7), and HU895B (8), are new, while two, micropeptins 478-A (10) and 478-B (11), were previously isolated from a bloom of M. aeruginosa from Japan. The new anabaenopeptin HU892 (9) belongs to the relatively rare subgroup, presenting an aliphatic amino acid at the carboxylic end of the peptide and N-methylhomoaromatic amino acid at the second position. The structures of the compounds were determined by 1D and 2D NMR techniques and mass spectrometric data. The isolated micropeptins inhibited trypsin with IC(50)'s that varied between 0.7 and 5.2 microM and unexpectedly inhibited chymotrypsin with IC(50)'s that varied between 2.8 and 72.0 microM. The SAR of these micropeptins is discussed.
Gesner-Apter
Shiri
S
Raymond and Beverly Sackler School of Chemistry and Faculty of Exact Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 69978, Israel.
Carmeli
Shmuel
S
D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007564:Japan; D046931:Microcystis / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013329:Structure-Activity Relationship; D014361:Trypsin Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014871:Water Microbiology
D047630:Depsipeptides; D014361:Trypsin Inhibitors; D002918:Chymotrypsin