Journal
MARINE DRUGS
Volume 15, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/md15090275
Keywords
fVIIa-sTF inhibitors; Microcystis; blood coagulation cascade; LC-MS; aeruginosin K-139; thrombin; micropeptin K-139; microviridin B
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Funding
- Prevention and Treatment Research Center for Thrombosis, Research Institute of Meijo University
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The rise of bleeding and bleeding complications caused by oral anticoagulant use are serious problems nowadays. Strategies that block the initiation step in blood coagulation involving activated factor VII-tissue factor (fVIIa-TF) have been considered. This study explores toxic Microcystis aeruginosa K-139, from Lake Kasumigaura, Ibaraki, Japan, as a promising cyanobacterium for isolation of fVIIa-sTF inhibitors. M. aeruginosa K-139 underwent reversed-phase solid-phase extraction (ODS-SPE) from 20% MeOH to MeOH elution with 40%-MeOH increments, which afforded aeruginosin K-139 in the 60% MeOH fraction; micropeptin K-139 and microviridin B in the MeOH fraction. Aeruginosin K-139 displayed an fVIIa-sTF inhibitory activity of similar to 166 mu M, within a 95% confidence interval. Micropeptin K-139 inhibited fVIIa-sTF with EC50 10.62 mu M, which was more efficient than thrombin inhibition of EC50 26.94 mu M. The thrombin/fVIIa-sTF ratio of 2.54 in micropeptin K-139 is higher than those in 4-amidinophenylmethane sulfonyl fluoride (APMSF) and leupeptin, when used as positive controls. This study proves that M. aeruginosa K-139 is a new source of fVIIa-sTF inhibitors. It also opens a new avenue for micropeptin K-139 and related depsipeptides as fVIIa-sTF inhibitors.
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