Folding of unstructured peptoids and formation of hetero-bimetallic peptoid complexes upon side-chain-to-metal coordination

Maria Baskin, Hui Zhu, Zheng Wang Qu, Jordan H. Chill, Stefan Grimme, Galia Maayan

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Helices are key structural features in biopolymers, enabling a variety of biological functions. Mimicking these secondary structure motifs has wide potential in the development of biomimetic materials. Peptoids, N-substituted glycine oligomers, are an important class of peptide mimics that can adopt polyproline type helices if the majority of their sequence consists of chiral bulky pendent groups. Such side-chains are structure inducers but they have no functional value. We present here the inclusion of several metal-binding groups in one peptoid oligomer as a new platform towards the development of functional helical peptoids. Thus, we describe the coordination of two metal ions to unstructured peptoids incorporating four 8-hydroxyquinoline (HQ) ligands at fixed positions as two (HQ, HQ) metal binding sites, and a mixture of chiral benzyl and alkyl substituents in varied positions along the peptoid backbone. For the first time, we demonstrate by circular dichroism spectroscopy, solution NMR techniques and high-level DFT calculations that some of these unstructured peptoids can fold upon metal binding to form helical structures. Replacing one HQ ligand with a terpyridine (Terpy) ligand resulted in unique sequences that can selectively coordinate Cu2+ to the (Terpy, HQ) and Zn2+ (or Co2+) to the (HQ, HQ) sites from a solution mixture containing Cu2+ and Zn2+ (or Co2+) ions. Interestingly, the binding of Cu2+ to the (Terpy, HQ) site in one of these peptoids can initiate a conformational change that in turn facilitates the coordination of Zn2+ (or Co2+) ions to the (HQ, HQ) site, demonstrating a unique example of positive allosteric cooperativity in peptide mimics.

Original languageEnglish
Pages (from-to)620-632
Number of pages13
JournalChemical Science
Volume10
Issue number2
DOIs
StatePublished - 14 Jan 2019

Bibliographical note

Publisher Copyright:
This journal is © The Royal Society of Chemistry.

Funding

The research leading to these results has received funding from the European Union's – Seventh Framework Program (FP7/ 2007–2013) under grant agreement no. 333034-MC–MF STRC AND FCN. G. M. and M. B. thank Mrs Larisa Panz for her assistance with the various MS measurements and Dr Boris Tumanskii for his assistance with the EPR measurements. M. B. thanks the Schulich foundation and the Gutwirth foundation for her PhD fellowship. S. G., H. Z. and Z. W. Q. thank the DFG for nancial support in the framework of the Leibniz price. J. C. acknowledges support of the Christians for Israel Chair for Medical Research.

FundersFunder number
European Union's – Seventh Framework ProgramFP7/ 2007–2013, 333034-MC
Gutwirth Foundation
Schulich foundation

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