Positive Allostery in Metal Ion Binding by a Cooperatively Folded Î²-Peptide Bundle Miller JP, Melicher MS, Schepartz A, J. Am. Chem. Soc., 2014, 136, 14726â€“14729.
Metal ion binding is exploited by proteins in nature to catalyze reactions, bind molecules, and favor discrete structures, but it has not been demonstrated in Î²-peptides or their assemblies. Here we report the design, synthesis, and characterization of a Î²-peptide bundle that uniquely binds two Cd(II) ions in a distinct bicoordinate array. The two Cd(II) ions bind with positive allosteric cooperativity and increase the thermodynamic stability of the bundle by more than 50 °C. This system provides a unique, synthetic context to explore allosteric regulation and should pave the way to sophisticated molecular assemblies with catalytic and substrate-sensing functions that have historically not been available to de novo designed synthetic proteomimetics in water.