Stabilization of Secondary Structure of Peptoid by Metal Coordination in Solution

Alisa Smolyakova, Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa, Israel
Galia Maayan, Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa, Israel

Secondary structure in folded biopolymers may be stabilized by a few different ways including hydrogen bonds formation, electrostatic interactions, Van der Waals forces, solvophobic interactions and metal coordination. Among these, intramolecular metal coordination is a powerful tool for constructing both a stable and a functional molecule. An example for the stabilization of most common helical structure of peptides, the α-helix, is by using side chains of histidine and cysteine residues in position i and i+4 which interact with transition metal ions. ^[1] Peptoids - oligomers of N-substituted glycine – can mimic the ability of peptides to fold into well-defined helical structures in solution. Since peptoids are not able to form hydrogen bonding the helical structures of peptoids is similar to polyproline type I helix with a pitch of 3 residues per turn. Thus we decided to use metal chelating ligands at positions i and i+3, chiral (S)-1-phenylethyl and (S)-1-methoxy-2-propyl N-substituted groups that provide helicity of structure and water solubility, respectively.^[2] By using the solid phase “sub-monomer” method^[3] we can effectively synthesize peptoids with different sequences of pedant groups in order to determinate the most stable helical peptoid. Solution state investigation methods, NMR spectroscopy and Circular Dichroism, provide evidence that most stable helical polyproline type I structure has peptoid with a bulky core

References:

1.      M. Reza Ghadiril and Chong Choi J. Am. Chem. Soc., 1990, 112, 1630-1632

2.      Galia Maayan, Michael D. Ward, Kent Kirshenbaum Chem.Commun. 2009, 56-58

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