Noncanonical Folding of Peptoid Oligomers: Formation of a Closed Conformation in Nonpolar Solvent

Jinyoung Oh; Min June Yang; Xingyu Chen; Juhye Shin; Bradley S Harris; Robert M Raddi; Suhyun Park; Marcel D Baer; Hohjai Lee; Chin-Ju Park; Vincent A Voelz; Jiwon Seo

doi:10.1021/acs.orglett.6c02040

Noncanonical Folding of Peptoid Oligomers: Formation of a Closed Conformation in Nonpolar Solvent

Jinyoung Oh
, Min June Yang
, Xingyu Chen
, Juhye Shin
, Bradley S Harris
, Robert M Raddi
, Suhyun Park
, Marcel D Baer
, Hohjai Lee
, Chin-Ju Park
, Vincent A Voelz
, Jiwon Seo

Cancer Signaling and Microenvironment (CSM)

Gwangju Institute of Science and Technology
Temple University
Physical and Computational Sciences Directorate
Department of Biomedicinal Chemistry
College of Science and Technology

Research output: Contribution to journal › Letter › peer-review

Abstract

Conformational behavior of peptoids in low-dielectric solvents remains poorly understood despite its relevance to membrane environments. Here, conformations of N-(S)-1-phenylethylglycine (Nspe) homo-oligomers were investigated in chloroform using NMR spectroscopy and MD simulations. Nspe₇ populated two closed conformations, while Nspe₁₀ adopted a single conformation reminiscent of the Nspe₉ threaded-loop structure. End-to-end hydrogen bonding and hydrophobic side-chain shielding stabilize these compact folds, minimizing polar surface area. These findings provide insights into peptoid folding in nonpolar media and solvent-directed conformational switching.

Original language	English
Pages (from-to)	8375-8381
Number of pages	7
Journal	Organic Letters
Volume	28
Issue number	26
Early online date	Jun 22 2026
DOIs	https://doi.org/10.1021/acs.orglett.6c02040 https://doi.org/10.1021/acs.orglett.6c02040
State	Published - Jul 3 2026

Keywords

Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Magnetic Resonance Spectroscopy
Molecular Conformation
Molecular Dynamics Simulation
Molecular Structure
Peptoids/chemistry
Protein Folding
Solvents/chemistry

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Oh, J., Yang, M. J., Chen, X., Shin, J., Harris, B. S., Raddi, R. M., Park, S., Baer, M. D., Lee, H., Park, C.-J., Voelz, V. A., & Seo, J. (2026). Noncanonical Folding of Peptoid Oligomers: Formation of a Closed Conformation in Nonpolar Solvent. Organic Letters, 28(26), 8375-8381. https://doi.org/10.1021/acs.orglett.6c02040, https://doi.org/10.1021/acs.orglett.6c02040

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title = "Noncanonical Folding of Peptoid Oligomers: Formation of a Closed Conformation in Nonpolar Solvent",

abstract = "Conformational behavior of peptoids in low-dielectric solvents remains poorly understood despite its relevance to membrane environments. Here, conformations of N-(S)-1-phenylethylglycine (Nspe) homo-oligomers were investigated in chloroform using NMR spectroscopy and MD simulations. Nspe7 populated two closed conformations, while Nspe10 adopted a single conformation reminiscent of the Nspe9 threaded-loop structure. End-to-end hydrogen bonding and hydrophobic side-chain shielding stabilize these compact folds, minimizing polar surface area. These findings provide insights into peptoid folding in nonpolar media and solvent-directed conformational switching.",

keywords = "Hydrogen Bonding, Hydrophobic and Hydrophilic Interactions, Magnetic Resonance Spectroscopy, Molecular Conformation, Molecular Dynamics Simulation, Molecular Structure, Peptoids/chemistry, Protein Folding, Solvents/chemistry",

author = "Jinyoung Oh and Yang, \{Min June\} and Xingyu Chen and Juhye Shin and Harris, \{Bradley S\} and Raddi, \{Robert M\} and Suhyun Park and Baer, \{Marcel D\} and Hohjai Lee and Chin-Ju Park and Voelz, \{Vincent A\} and Jiwon Seo",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors. Published by American Chemical Society.",

year = "2026",

month = jul,

day = "3",

doi = "10.1021/acs.orglett.6c02040",

language = "English",

volume = "28",

pages = "8375--8381",

journal = "Organic Letters",

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publisher = "American Chemical Society",

number = "26",

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TY - JOUR

T1 - Noncanonical Folding of Peptoid Oligomers

T2 - Formation of a Closed Conformation in Nonpolar Solvent

AU - Oh, Jinyoung

AU - Yang, Min June

AU - Chen, Xingyu

AU - Shin, Juhye

AU - Harris, Bradley S

AU - Raddi, Robert M

AU - Park, Suhyun

AU - Baer, Marcel D

AU - Lee, Hohjai

AU - Park, Chin-Ju

AU - Voelz, Vincent A

AU - Seo, Jiwon

PY - 2026/7/3

Y1 - 2026/7/3

N2 - Conformational behavior of peptoids in low-dielectric solvents remains poorly understood despite its relevance to membrane environments. Here, conformations of N-(S)-1-phenylethylglycine (Nspe) homo-oligomers were investigated in chloroform using NMR spectroscopy and MD simulations. Nspe7 populated two closed conformations, while Nspe10 adopted a single conformation reminiscent of the Nspe9 threaded-loop structure. End-to-end hydrogen bonding and hydrophobic side-chain shielding stabilize these compact folds, minimizing polar surface area. These findings provide insights into peptoid folding in nonpolar media and solvent-directed conformational switching.

AB - Conformational behavior of peptoids in low-dielectric solvents remains poorly understood despite its relevance to membrane environments. Here, conformations of N-(S)-1-phenylethylglycine (Nspe) homo-oligomers were investigated in chloroform using NMR spectroscopy and MD simulations. Nspe7 populated two closed conformations, while Nspe10 adopted a single conformation reminiscent of the Nspe9 threaded-loop structure. End-to-end hydrogen bonding and hydrophobic side-chain shielding stabilize these compact folds, minimizing polar surface area. These findings provide insights into peptoid folding in nonpolar media and solvent-directed conformational switching.

KW - Hydrogen Bonding

KW - Hydrophobic and Hydrophilic Interactions

KW - Magnetic Resonance Spectroscopy

KW - Molecular Conformation

KW - Molecular Dynamics Simulation

KW - Molecular Structure

KW - Peptoids/chemistry

KW - Protein Folding

KW - Solvents/chemistry

UR - https://www.scopus.com/pages/publications/105043824917

U2 - 10.1021/acs.orglett.6c02040

DO - 10.1021/acs.orglett.6c02040

M3 - Letter

C2 - 42332885

SN - 1523-7060

VL - 28

SP - 8375

EP - 8381

JO - Organic Letters

JF - Organic Letters

IS - 26

ER -

Noncanonical Folding of Peptoid Oligomers: Formation of a Closed Conformation in Nonpolar Solvent

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Keywords

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