Templating α-amylase peptide inhibitors with organotin compounds

Metal centers have been widely used to nucleate secondary structures in linear peptides. However, very few examples have been reported for peptide/organometal complexes. Here, we illustrate the use of organotin compounds as nucleation centers for secondary structures of linear peptide inhibitors of α-amylase. Specifically, we utilized methyl-substituted tin compounds to template short type I β-turns similar to the binding loop of tendamistat, the natural inhibitor of the enzyme, which are able to bind and inhibit α-amylase. We show that enzyme activity is inhibited by neither the unstructured peptide nor the organotin compounds, but rather the peptide/organotin complex, which inhibits the enzyme with K _i ~ 0.5 μM. The results delineate a strategy to use organometallic compounds to drive the active conformation in small linear peptides.