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

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.

SUBMITTER: Baskin M

PROVIDER: S-EPMC6334629 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

Baskin Maria M Zhu Hui H Qu Zheng-Wang ZW Chill Jordan H JH Grimme Stefan S Maayan Galia G

Chemical science 20181017 2

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, <i>N</i>-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 t ...[more]

PMID: 30713653

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Project description:The ability to design foldamers that mimic the defined structural motifs of natural biopolymers is critical for the continued development of functional biomimetic molecules. Peptoids, or oligomers of N-substituted glycine, represent a versatile class of foldamers capable of folding into defined secondary and tertiary structures. However, the rational design of discretely folded polypeptoids remains a challenging task, due in part to an incomplete understanding of the covalent and noncovalent interactions that direct local peptoid folding. We have found that simple, peptoid monomer model systems allow for the effective isolation of individual interactions within the peptoid backbone and side chains and can facilitate the study of the role of these interactions in restricting local peptoid conformation. Herein, we present an analysis of a set of peptoid monomers and an oligomer containing N-aryl side chains capable of hydrogen bonding with the peptoid backbone. These model peptoids were found to exhibit well-defined local conformational preferences, allowing for control of the ?, ?, and ? dihedral angles adopted by the systems. Fundamental studies of the peptoid monomers enabled the design and synthesis of an acyclic peptoid reverse-turn structure, in which N-aryl side chains outfitted with ortho-hydrogen bond donors were hypothesized to play a critical role in the stabilization of the turn. This trimeric peptoid was characterized by X-ray crystallography and 2D NMR spectroscopy and was shown to adopt a unique acyclic peptoid reverse-turn conformation. Further analysis of this turn revealed an n??*(C?O) interaction within the peptoid backbone, which represents the first reported example of this type of stereoelectronic interaction occurring exclusively within a polypeptoid backbone. The installation of N-aryl side chains capable of hydrogen bonding into peptoids is straightforward and entirely compatible with current solid-phase peptoid synthesis methodologies. As such, we anticipate that the strategic incorporation of these N-aryl side chains should facilitate the construction of peptoids capable of adopting discrete structural motifs, both turnlike and beyond, and will facilitate the continued development of well-folded peptoids.

Dataset Information

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

Publications

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

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