Peptoid Oligomers as Unique Chelators for Metal Ions towards Biomimetic Applications such as Recognition, Folding and Cooperativity

Maria Baskin mariabaskin88@gmail.com 1 Hui Zhu 2 Jordan Chill 3 Stefan Grimme 2 Galia Maayan 1
1Schulich Faculty of Chemistry, Technion- Israel Institute of Technology, Haifa, Israel
2Mulliken Center for Theoretical Chemistry, University of Bonn, Bonn, Germany
3Department of Chemistry, Bar Ilan University, Ramat Gan, Israel

Metal ions play a significant role in the activity of biological systems including catalysis, recognition and folding. This research focuses on the interactions of metal ions with peptoids – N-substituted glycines, which are a family of peptidomimetic foldamers capable of adopting stable secondary structures in solution if chiral bulky groups are incorporated within the peptoid sequence. Thus, 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. Peptoids are synthesized efficiently using the solid phase submonomer method which enables facile incorporation of a wide variety of side chains resulting in high diversity of the peptoid sequence. The objective of this research is to gain new insights regarding the interactions between metal ions and peptoids, as tools for structural studies and biomimetic applications. This work includes rational design, synthesis and characterization of unique metal-binding peptoids for biomimetic applications such as folding, recognition1 and cooperativity. In terms of folding, we decided to investigate whether metal coordination can be used to induce helical structure of peptoids lacking chiral bulky groups. To this aim, several unstructured peptoids bearing metal-binding ligands at positions i and i+3 were synthesized efficiently using the solid phase submonomer method. Using Circular Dichroism and NMR spectroscopy we provide strong evidences for the folding of peptoids by metal coordination. In addition, we wished to explore if intramolecular metal binding of one metal ion in a rational designed peptoid, can result in well-organized environment for enhanced binding of different metal ion at distinct binding site, namely cooperative metal binding. For this aim, we synthesized a peptoid bearing two distinct intramolecular metal binding sites and we demonstrate, by comparison between association constants with control peptoids, a cooperative metal binding of Co2+ to one specific binding site after coordination of Cu2+ to another binding site due to structural changes.

Reference:

  1. Baskin and G. Maayan, Chem. Sci. 2016, 7, 2809-2820.









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