This article reviews recent advances in the design and discovery of inert metal complexes as protein binders. In these metal-based probes or drug candidates, the metal is supposed to exert a purely structural role by organizing the coordinating ligands in the three dimensional space to achieve a shape and functional group complementarity with the targeted protein pockets. Presented examples of sandwich, half-sandwich and octahedral d(6)-metal complexes reinforce previous perceptions that metal complexes are highly promising scaffolds for the design of small-molecule protein binders and complement the molecular diversity of organic chemistry by opening untapped chemical space.
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