Microginins 299-A (1 and -B (2) have been iscdated from the cyanobacterium MicroQ,stis aeruginosa . Their structures were determined by tw(~-dimensional I H-iH and iH-i'~c NMR correlation experimems and confirmed by mass spectral and amino acid analyses, Their absolute stereochemistries were deduced by a combination of spectral and chemical studies. I and 2 inhibited leucine aminopeptidase with ICso's of 4.6 and 6.5 lag/mE respectively. โข ~ 1997 Elsevier Science Ltd.
Microcystis aeruginosa produces some unique and interesting bioactive peptides. I Noteworthy examples are hepatotoxic cyclicpeptides microcystins 2 and nontoxic cyclic depsipeptides micropeptins 3 and microviridins, 4 which inhibit serine proteases such as plasmin, trypsin, elastase or chymotrypsin. As part of continuing search for protease inhibitors from cyanobacteria, we have described a novel linear pentapeptide microginin, which inhibits angiotensin-converting enzymes from M. aeruginosa (NIES-100). 5 We report here the isolation and structure elucidation of congeners to microginin, microginins 299-A (1) and -B (2) (Fig. ), which inhibit leucine aminopeptidase, from M. aeruginosa (NIES-299).
M. aeruginosa (NIES-299) 6 was isolated from a bloom in Lake Kasumigaura and mass-cultured in our laboratory as previously described. 7 The 80% methanol extract of freeze-dried alga was partitioned between water and diethyl ether. The aqueous layer was further extracted with n-butanol and fractionated by ODS flash column chromatography (20-100% MeOH elution) followed by reversed-phase HPLC, using 0.05% TFA in 35% MeCN to yield microginins 299-A (1, 70 mg) and -B (2, 144 mg) as colorless amorphous powders.
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