Unveiling the conformational landscape of achiral all-<i>cis tert</i>-butyl β-peptoids

Angelici, Gaetano; Bhattacharjee, Nicholus; Pypec, Maxime; Jouffret, Laurent; Didierjean, Claude; Jolibois, Franck; Perrin, Lionel; Roy, Olivier; Taillefumier, Claude

doi:10.1039/d2ob01351g

Cited by 3 publications

(2 citation statements)

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“…It is worth noting that multiple force fields are available in the protein space, but that field is significantly more developed and studied. Despite this higher bar to entry, peptoid simulation papers include at least 19 GAFF-based, ,,− 13 MFTOID-, ,− 11 CHARMM-, or CGenFF-based, − 3 PEPDROID-based, − and other computational studies. − One particularly noteworthy effort was the development of a peptoid rotamer library containing over 50 side chains in the structural prediction tool ROSETTA based on CHARMM peptide parameters. , …”

Section: Introductionmentioning

confidence: 99%

Development of a Systematic and Extensible Force Field for Peptoids (STEPs)

2023

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Peptoids (N-substituted glycines) are a class of biomimetic polymers that have attracted significant attention due to their accessible synthesis and enzymatic and thermal stability relative to their naturally occurring counterparts (polypeptides). While these polymers provide the promise of more robust functional materials via hierarchical approaches, they present a new challenge for computational structure prediction for material design. The reliability of calculations hinges on the accuracy of interactions represented in the force field used to model peptoids. For proteins, structure prediction based on sequence and de novo design has made dramatic progress in recent years; however, these models are not readily transferable for peptoids. Current efforts to develop and implement peptoid-specific force fields are spread out, leading to replicated efforts and a fragmented collection of parameterized sidechains. Here, we developed a peptoid-specific force field containing 70 different side chains, using GAFF2 as starting point. The new model is validated based on the generation of Ramachandran-like plots from DFT optimization compared against force field reproduced potential energy and free energy surfaces as well as the reproduction of equilibrium cis/trans values for some residues experimentally known to form helical structures. Equilibrium cis/trans distributions (Kct) are estimated for all parameterized residues to identify which residues have an intrinsic propensity for cis or trans states in the monomeric state.

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Section: Introductionmentioning

confidence: 99%

Development of a Systematic and Extensible Force Field for Peptoids (STEPs)

2023

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“…In addition, due to the presence of an extra CÀ C bond in the backbone, the β-peptoids contain a greater number of rotatable bonds (Figure 1A); angles ω, Θ, φ and Ψ) that can increase their flexibility. Sidechains such as N-(S)-naphthylethyl that induce cis-amide geometries in αpeptoids, [21,[26][27][28][29][30] also enforce cis-amide geometries in β-peptoids (Figure 1B). [23,28] Morimoto et al have shown that incorporation of a naphthyl group in the backbone β-carbon restrained the ω and φ angles (Figure 1C) of the β-peptoids.…”

Section: Introductionmentioning

confidence: 99%

Conformational Studies of β‐Azapeptoid Foldamers: A New Class of Peptidomimetics with Confined Dihedrals

Anshulata,

Vishnoi,

Kanta Sarma

2023

Chemistry A European J

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Controlling amide bond geometries and the secondary structures of β‐peptoids is a challenging task as they contain several rotatable single bonds in their backbone. Herein, we describe the synthesis and conformational properties of novel “β‐azapeptoids” with confined dihedrals. We discuss how the acylhydrazide sidechains in these molecules enforce trans amide geometries (ω ~ 180⁰) via steric and stereoelectronic effects. We also show that the Θ(Cα‐Cβ) and Ψ(OC‐Cα) backbone torsions of β‐azapeptoids occupy a narrow range (170‐180⁰) that can be rationalized by the staggered conformational preference of the backbone methylene carbons and a novel backbone nO → σ*Cβ‐N interaction discovered in this study. However, the φ (Cβ‐N) torsion remains freely rotatable and, depending on φ, the sidechains can be parallel, perpendicular, and anti‐parallel relative to each other. In fact, we observed parallel and perpendicular relative orientations of sidechains in the crystal geometries of β‐azapeptoid dimers. We show that φ of β‐azapeptoids can be controlled by incorporating a bulky substituent at the backbone β‐carbon, which could provide complete control over all the backbone dihedrals. Finally, we show that the φ and Ψ dihedrals of β‐azapeptoids resemble that of a PPII helix and they retain PPII structure when incorporated in Host‐Guest proline peptides.

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