Tuning conformation and properties of peptidomimetic backbones through dual <i>N</i>/<i>C</i><sub>α</sub>-substitution

Kaminker, Revital; Kaminker, Ilia; Gutekunst, Will R.; Luo, Yingdong; Lee, Sang‐Ho; Niu, Jing; Han, Songi; Hawker, Craig J.

doi:10.1039/c8cc01356j

“…All the 1-5 mer of NSAs were obtained with decent yields (Figure 3b, S5-8). There have been reports about oligo-NSGs containing skipped NSA residues 7,19,[29][30][31][32][33] but this is the first report of isolation of optically pure oligo-NSAs containing consecutive NSA residues with N-substituents other than methyl. 1H and 13C NMR spectra are shown on Figure S7 and S8.…”

Section: Synthesismentioning

confidence: 91%

A Peptoid with Extended Shape in Water

Morimoto¹,

Fukuda²,

Watanabe³

et al. 2019

Preprint

0

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<div> <div> <div> <p>“Peptoids” was proposed, over decades ago, as a term describing analogs of peptides that exhibit better physicochemical and pharmacokinetic properties than peptides. Oligo-(N-substituted glycines) (oligo-NSG) was previously proposed as a peptoid due to its high proteolytic resistance and membrane permeability. However, oligo-NSG is conformationally flexible and is difficult to achieve a defined shape in water. This conformational flexibility is severely limiting biological application of oligo-NSG. Here, we propose oligo-(N-substituted alanines) (oligo-NSA) as a new peptoid that forms a defined shape in water. A synthetic method established in this study enabled the first isolation and conformational study of optically pure oligo-NSA. Computational simulations, crystallographic studies and spectroscopic analysis demonstrated the well-defined extended shape of oligo-NSA realized by backbone steric effects. The new class of peptoid achieves the constrained conformation without any assistance of N-substituents and serves as an ideal scaffold for displaying functional groups in well-defined three-dimensional space, which leads to effective biomolecular recognition. </p> </div> </div> </div>

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“…However, they also incorporated NSA alternately, not consecutively. 35 36 Inspired by the reports by Kodadek and other pioneers, we initiated a more detailed conformational analysis of oligo NSA.…”

Section: Proposal Of Oligo Nsa As a Conformationallymentioning

confidence: 99%

Peptoids with Substituents on the Backbone Carbons as Conformationally Constrained Synthetic Oligoamides

Morimoto¹,

Sando

²

2020

J. Synth. Org. Chem. Jpn.

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Oligo(N substituted glycine) (oligo NSG), also known as peptoid, is a synthetic oligomer with high proteolytic stability and membrane permeability due to the N substituted structures. These bene cial pharmacokinetic properties make the oligomer attractive for biological applications. However, its conformational exibility limits its utilization as protein ligands. Recently, the introduction of backbone substituents to oligo NSG has been demonstrated to restrict its own backbone bond rotations via steric interactions, and the resulting oligo(N substituted alanine) (oligo NSA) has been demonstrated to be a conformationally constrained oligomer. Here, we review the concept, history, synthetic methodologies, conformational analysis, and biological applications of the new synthetic oligomer. We also conducted overview research on N substituted peptides consisting of non α amino acid residues to facilitate the plausible future expansion of the conformationally constrained peptoids of diverse three dimensional structures.

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“…This is consistent with the previous report that oligo-NSGs with alternate NSA residues are intrinsically disordered. 30…”

Section: X-ray Crystallographic Study and Molecular Dynamics Simulationsmentioning

confidence: 99%

A Peptoid with Extended Shape in Water

Morimoto¹,

Fukuda²,

Watanabe³

et al. 2019

Preprint

0

View full text Add to dashboard Cite

<div> <div> <div> <p>“Peptoids” was proposed, over decades ago, as a term describing analogs of peptides that exhibit better physicochemical and pharmacokinetic properties than peptides. Oligo-(N-substituted glycines) (oligo-NSG) was previously proposed as a peptoid due to its high proteolytic resistance and membrane permeability. However, oligo-NSG is conformationally flexible and is difficult to achieve a defined shape in water. This conformational flexibility is severely limiting biological application of oligo-NSG. Here, we propose oligo-(N-substituted alanines) (oligo-NSA) as a new peptoid that forms a defined shape in water. A synthetic method established in this study enabled the first isolation and conformational study of optically pure oligo-NSA. Computational simulations, crystallographic studies and spectroscopic analysis demonstrated the well-defined extended shape of oligo-NSA realized by backbone steric effects. The new class of peptoid achieves the constrained conformation without any assistance of N-substituents and serves as an ideal scaffold for displaying functional groups in well-defined three-dimensional space, which leads to effective biomolecular recognition. </p> </div> </div> </div>

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Tuning conformation and properties of peptidomimetic backbones through dual N/C_α-substitution

Cited by 17 publications

References 37 publications

A Peptoid with Extended Shape in Water

A Peptoid with Extended Shape in Water

Peptoids with Substituents on the Backbone Carbons as Conformationally Constrained Synthetic Oligoamides

A Peptoid with Extended Shape in Water

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Tuning conformation and properties of peptidomimetic backbones through dual N/Cα-substitution

Cited by 17 publications

References 37 publications

A Peptoid with Extended Shape in Water

A Peptoid with Extended Shape in Water

Peptoids with Substituents on the Backbone Carbons as Conformationally Constrained Synthetic Oligoamides

A Peptoid with Extended Shape in Water

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Product

Resources

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Tuning conformation and properties of peptidomimetic backbones through dual N/C_α-substitution