cis-Amide promotion in α-ABpeptoid foldamers via triazolium side chains.

Abstract

Precise control of amide bond rotation is crucial for the construction of well-defined three-dimensional structures in peptidomimetic foldamers. We previously introduced α-ABpeptoids as a new class of peptoid foldamers incorporating backbone chirality and demonstrated their folding propensities. However, the rotational isomerism of their backbone amide bonds remains largely unregulated. Here, we report the development of α-ABpeptoids functionalized with triazolium side chains that promote cis-amide bond formation. A series of α-ABpeptoid oligomers bearing neutral triazole or cationic triazolium side chains were synthesized and analyzed by NMR and circular dichroism spectroscopy. The triazolium-functionalized α-ABpeptoids exhibited a strong preference for cis-amide geometry, resulting in enhanced conformational homogeneity. These findings establish triazolium substitution as an effective strategy for conformational control in α-ABpeptoid foldamers, expanding their utility in the design of structured, functional peptidomimetics.