Synthesis and Conformational Analysis of Quinoline–Oxazole Peptides

Abstract

AbstractThe incorporation of flexible aliphatic units into otherwise rigid aromatic foldamer sequences may result in different outcomes. The flexible units may have conformational preferences of their own that can be expressed orthogonally to those of the aromatic units. Alternatively, the latter may dictate their folding behavior onto the former. Hybrid aliphatic–aromatic peptidic oligomers combining oxazole‐based (O) and quinoline‐based (Q) amino acids have been synthesized, and their folding behavior has been investigated in solution by NMR spectroscopy and CD spectroscopy, and in the solid state by X‐ray crystallography. Sequences based on the OQQ repeat motif were shown to fold into a canonical aromatic helix motif dominated by the preferences of the quinoline, whereas sequences based on OQ repetitions preferred to fold into a herringbone helix in which the conformational preference of the oxazole units is also expressed.