Solution structure of the human endostatin fragment EH6-49 by 1-H NMR and molecular dynamics calculations

摘要

The inhibition of tumour vascularisation is one strategy for the development of new anticancer agents currently under investigation.Endostatin is a potent endogeneous inhibitor of angiogenesis,produced by cleavage of collagen XVIII.Recently,a family of peptides has been synthesised and some of them have shown to maintain the same level of anti-angiogenic activity observed for endostatin.A pro-angiogenic activity was also observed depending on which endostatin segment is taken into consideration.It is not clear,at the moment,the molecular basis of the biological activity of endostatin or of their synthetic fragments.A recent finding has indicated a beta 1-integrin and heparin-dependent mechanism.Endostatin itself is also found in one insoluble form,able of self-reorganisation and with amyloidogenic properties.Other amyloid forming peptides,such as the beta-peptide,have similar properties and this feature might constitute a common feature of all anti-angiogenic peptides.