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Unification of the copper(I) binding affinities of the metallo-chaperones Atx1, Atox1, and related proteins

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The mechanism is fundamentally different

For example, the compound 13 (racemic) is a very week IRAP inhibitor (Lukaszuk et al., 2011) and compound 14 with a 4-hydroxydiphenylmethane scaffold as a substitute for Tyr 2 is essentially inactive (Figure 4) ( 1 is essential and the proper orientation of the Tyr 2 side chain in space is critical for activity and IRAP inhibition while various alternations and topography at the C-terminal are more acceptable

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