title: Templating α-amylase peptide inhibitors with organotin compounds.
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.
authors: Department for Innovation in Biological, Agro-Food and Forest Systems, University of Tuscia, Viterbo, Italy. porcelli@unitus.it
authors: Fernando
authors: F
authors: Porcelli
authors: Cristina
authors: C
authors: Olivieri
authors: Larry R
authors: LR
authors: Masterson
authors: Yi
authors: Y
authors: Wang
authors: Gianluigi
authors: G
authors: Veglia
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D009479:Neuropeptides / Q000737:chemistry; D009947:Organotin Compounds / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D000516:alpha-Amylases / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D009479:Neuropeptides; D009947:Organotin Compounds; D010455:Peptides; C075692:stannin; D000516:alpha-Amylases; C030526:tendamistate