Sequence-specific, monodisperse peptoids, N-substituted glycine oligomers, have found diverse utility in biological and materials applications. A foundational understanding of residues that promote peptoid structure by influencing cis-trans amide bond equilibria has emerged. Nonetheless, few studies of water-soluble peptoid structures are available. Access to short, water-soluble peptoids with well- defined three-dimensional structures will advance the functional repertoire of peptoids.

In this work, we will present our systematic study of the structures of water soluble 6-mer peptoids. These peptoids include both aromatic and polar, charged residues sequenced in a putative amphiphilic ordering. Residues include both aromatic and polar groups that exhibit an energetic preference for the cis-amide conformation and are thus expected to promote a helical peptoid structure. Structures of the synthesized peptoid oligomers have been studied by CD spectroscopy and NMR spectroscopy in a range of aqueous solution conditions to evaluate both sequence and environmental contributions to structural ordering.

We have observed that the positioning of the aromatic residues in the peptoid sequence has a pronounced influence on peptoid structure; when residues are at the N-terminal and fourth position in the sequence, the structural ordering is different than when these residues are placed at other i, i + 3 positions in the sequence. The effects of aromatic residue identity and the identity of polar residues on peptoid structures will also be compared and presented.

This work will build a foundation of understanding about peptoid sequence-structure relationships; we and others will build on this to design and study water-soluble peptoids with varied functions.