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.
Templating α-amylase peptide inhibitors with organotin compounds / F. Porcelli, C. Olivieri, L.R. Masterson, Y. Wang, G. Veglia. - In: JBIC. - ISSN 0949-8257. - 16:8(2011 Dec), pp. 1197-1204. [10.1007/s00775-011-0808-5]
Templating α-amylase peptide inhibitors with organotin compounds
C. OlivieriSecondo
;
2011
Abstract
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.File | Dimensione | Formato | |
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