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Furthermore, compound 16 is degraded considerably more slowly in membrane preparations than Ang IV and stimulates proliferation of mouse neural stem cells at low concentrations, supporting a role of IRAP in neurogenesis ( 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)