The design of protein-protein interactions and the generation of new chemical functions in proteins both are challenging goals in chemistry.  We have devised an approach (Metal Templated Interface Design) that combines both goals, in which protein self-assembly is first directed by metal coordination, followed by the redesign of the interfaces formed around the metals for new metal-based functions. Here we describe how a Zn-templated tetrameric protein assembly can be stabilized through a combination of non-covalent and covalent interactions to create a stable macrocyclic ligand platform. Our study shows that multiple disulfide bonds can be correctly formed under the direction of metal coordination, and how the resulting macrocyles can stably harbor several different metal ions (or their oxidation states) whose reactivities are currently under examination.

Metal-templated design of protein macrocycles

243rd National Meeting (2012)

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