Templating α-amylase peptide inhibitors with organotin compounds

J Biol Inorg Chem. 2011 Dec;16(8):1197-204. doi: 10.1007/s00775-011-0808-5. Epub 2011 Jul 7.

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.

MeSH terms

  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Kinetics
  • Models, Molecular*
  • Molecular Conformation
  • Neuropeptides / chemistry
  • Organotin Compounds / chemistry*
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Protein Conformation
  • alpha-Amylases / antagonists & inhibitors*
  • alpha-Amylases / chemistry*

Substances

  • Enzyme Inhibitors
  • Neuropeptides
  • Organotin Compounds
  • Peptides
  • stannin
  • alpha-Amylases
  • tendamistate