Formation of Secondary Structure of Unstructured Peptoids by Metal Coordination

Maria Baskin, Schulich Faculty of Chemistry, Technion, Haifa, Israel
Galia Maayan, Schulich Faculty of Chemistry, Technion, Haifa, Israel

Metal ions play a significant role in the activity of biological systems including catalysis, recognition and folding. In the context of folding, it has been shown that intramolecular metal ligation is a useful method for stabilization of helical structures, especially in short peptides. This stabilization can be done by connecting two residues, which are located at positions i and i+4 of the peptide strand via metal coordination.^{1, 2} Peptoids- oligomers of N-substituted glycine, are a family of peptidomimetic foldamers capable of adopting stable secondary structures if bulky chiral side chains are incorporated into the oligomer sequence.  Helical secondary structure of peptoids is forced due to local steric and stereoelectronic interactions and mostly resembles that of the polyproline-type I helix, with a pitch of three residues per turn. Herein, we decided to mimic the ability of metal ions to stabilize secondary structure of metallopeptides and investigate whether metal coordination can induce helical structure of peptoids. To this aim, several unstructured peptoids bearing metal-binding ligands at positions i and i+3 were synthesized by an efficient solid-phase method (the sub-monomer approach).³  Using Circular Dichroism and NMR spectroscopy we provide strong evidences for the folding of peptoids by metal coordination.

References:

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2.      Ghadiri, M. R., Fernholz, A. K., J. Am. Chem. Soc. 1990, 112, 9633-9635.

3.      Zuckermann, R. N., Kerr, J. M ., Kent, S. B.H., Moos, W.H., J. Am. Chem. Soc., 1992, 114, 10646.