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.