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Figure 5 Contrary to the results obtained after modification in the C-terminal of Ang IV where essentially all compounds examined exhibited some activity, oxidative cyclization of the side chains of Cys 1 and Cys 3 and consequently creation of an 11-membered disulfide macrocycle in the N-terminal rendered the inactive compound 20 (Figure 6)

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Such ligand-induced dimerization model has been observed in the activation of c-MET by a bacterial c-MET agonistInlB 31 , as well as in the activation of many other RTKs, such as PDGFR and VEGFR 32,33

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