Angiostatin
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Angiostatin is a natural angiogenesis inhibitor that is currently underlying clinical trials for its use in anticancer therapy. It blocks the growth of new blood vessels.
Angiostatin is a 57 kDa multimodular fragment of a larger protein, plasminogen. It consists of various isoforms including from three to five contiguous Kringle modules. Each module contains two small beta sheets and three disulfide bonds.
Angiostatin is produced by autoproteolytic cleavage of plasminogen, involving extracellular disulfide bond reduction by phosphoglycerate kinase.
Angiostatin is known to bind a lot of proteins, especially to angiomotin and endothelial cell surface ATP synthase but also integrins, annexin II, C-met receptor, NG2-proteoglycans, tissue-type plasminogen activator, chondroitin sulfate proteoglycans, and CD26. Also smaller fragments of angiostatin has been shown to bind several other proteins. There is still considerable uncertainty on its mechanism of action, but it seems to involve for example inhibition of endothelial cell migration, proliferation and induction of apoptosis .