Residue-based program of a β-peptoid twisted strand shape <i>via</i> a cyclopentane constraint

Kim, Jungyeon; Kobayashi, Hiroka; Yokomine, Marin; Shiratori, Yota; Ueda, Takumi; Takeuchi, Koh; Umezawa, Koji; Kuroda, Daisuke; Tsumoto, Kouhei; Morimoto, Jumpei; Sando, Shinsuke

doi:10.1039/d2ob01300b

Cited by 5 publications

(5 citation statements)

References 44 publications

(73 reference statements)

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“…The bottomup approach for the peptide nanoshape design is more direct and straightforward compared to the design approach in proteins and foldamers [30][31][32] which are globally stabilized by a network of interresidual interactions. The introduction of additional building blocks, such as a proline residue and Nsubstituted b-amino acid residues 33 , would further increase the peptide nanoshape diversity in the future. It would realize the peptide nanoshape diversity equal to or even larger than that realized by proteins.…”

Section: Discussionmentioning

confidence: 99%

Bottom-up design of peptide nanoshapes in water using oligomers of N-methyl-L/D-alanine

Morimoto

Shiratori

Yokomine

et al. 2023

Preprint

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De novo design of peptide nanoshapes is of great interest in biomolecular science since the local peptide nanoshapes formed by a short peptide chain in the proteins are often key to the biological activities. Here, we show that the de novo design of peptide nanoshapes with sub-nanometer conformational control can be realized using peptides consisting of N-methyl-L-alanine and N-methyl-D-alanine residues as studied by NMR, X-ray and XFEL crystallographic and computational analyses as well as by direct imaging of the dynamics of the peptide’s nanoshape using cinematographic electron microscopic technique. The conformation of N-methyl-L/D-alanine residue is largely fixed because of the restricted bond rotation, and hence can serve as a scaffold on which we can build a peptide into a designed nanoshape. The local shape control by per-residue conformational restriction by torsional strains starkly contrasts with the global shape stabilization of proteins based on many remote interactions. The oligomers allow the bottom-up design of diverse peptide nanoshapes with a small number of amino acid residues and would offer unique opportunities to realize the de novo design of biofunctional molecules, such as catalysts and drugs.

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Section: Discussionmentioning

confidence: 99%

Bottom-up design of peptide nanoshapes in water using oligomers of N-methyl-L/D-alanine

Morimoto

Shiratori

Yokomine

et al. 2023

Preprint

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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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“…[20] In recent years, several strategies were developed to control their amide bond conformation by using sidechains with unique steric and stereoelectronic features. [21] In contrast to α-peptoids, the β-peptoids [22][23][24][25] are less studied. The submonomer synthesis steps of β-peptoids are less efficient than α-peptoids.…”

Section: Introductionmentioning

confidence: 99%

“…[24] Recently, the authors achieved control over all four dihedral angles (ω, φ, Ψ and Θ) of β-peptoids by using constrained cyclopentane units in the backbone (Figure 1D). [25] Surprisingly, the sidechains that are known to induce trans amide geometries in αpeptoids [21,[31][32][33][34][35] were rarely investigated in β-peptoids. In an earlier study, [36] we discussed the stabilization of trans amide conformations in α-azapeptoids derived from acylhydrazides and analogous submonomers (Figure 1E).…”

Section: Introductionmentioning

confidence: 99%

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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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Residue-based program of a β-peptoid twisted strand shape via a cyclopentane constraint

Abstract: N-Substituted peptides, such as peptoids and β-peptoids, have been reported to have unique structures with diverse functions, like catalysis and manipulation of biomolecular functions. Recently, the preorganization of monomer shape...

Cited by 5 publications

References 44 publications

Bottom-up design of peptide nanoshapes in water using oligomers of N-methyl-L/D-alanine

Bottom-up design of peptide nanoshapes in water using oligomers of N-methyl-L/D-alanine

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

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

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