Two Helical Conformations from a Single Foldamer Backbone: “Split Personality” in Short α/β‐Peptides

Abstract

Oligomers that adopt predictable conformations ("foldamers") are subjects of increasing interest from the perspectives of both fundamental research and applications.[1] The study of unnatural oligomers that display secondary structures analogous to those of proteins or nucleic acids provides new insight on the parameters that influence the "foldability" of a backbone, e.g., the relationships between conformational stability and number of residues or residue flexibility. As the rules that govern shape are elucidated for new backbones, this

Interplay among side chain sequence, backbone composition, and residue rigidification in polypeptide folding and assembly

“…Such efforts have included the study of RNA analogues based on pyranose rather than furanose (3), peptides based on ␤-or ␥-amino acids rather than ␣-amino acids (4,5), and systems that diverge more profoundly from biological precedents (6,7). As the folding propensities of new backbone elements have been elucidated, the first steps have been taken to blend natural and unnatural subunits and thereby create folded oligomers with heterogeneous backbones and distinctive behavior (8)(9)(10).…”

Protein and peptide biomimicry: Gold‐mining inspiration from Nature's ingenuity

“…Examples of well-characterized foldamer scaffolds, shown in Figure 1, include a/b peptides, 3 b-peptides and g-peptides, 4 N-substituted glycines (peptoids), 2,5 phenylene ethynylenes, 6 and urea derivatives. 7 All of these classes of non-natural oligomers have been shown to exhibit kinetic and thermodynamic stability, and can mimic some functions of bioactive peptides.…”

“…A hybrid structure with a heterogeneous backbone can also be formed using a combination of a-peptide and b-peptide monomers in the same molecule. 3 Sporadic inclusion of b-peptide residues can induce turns, and can cause minor changes to foldamer structure. 10 Molecules with a regularly repeating arrangement of a-and b-peptide monomers have been made and found to form stable structures closely related to those of natural peptides.…”

“…10 Molecules with a regularly repeating arrangement of a-and b-peptide monomers have been made and found to form stable structures closely related to those of natural peptides. 3 Peptoid structure is isomerically related to that of peptides, in that the side chains are attached to amide nitrogens rather than to a-carbons, as shown in Figure 1. 5 The conformational and stereochemical ramifications of the N-substituent on the peptoid backbone (which is identical to a peptide backbone in its sequence of atoms) are significant.…”

Pyrrolidinyl peptide nucleic acid with α/β-peptide backbone

“…26 Recently, oligomers with α/β peptide backbone were recognized as a potential foldamer system due to their well defined helical conformation. [27][28][29] We have recently developed a new class of pyrrolidinyl PNA consisting of an alternate sequence (acpc) part, namely (1S,2S)-, (1S,2R)-, (1R,2R)-and (1R,2S)-, but with the same (2'R,4'R)-configuration of the pyrrolidine part were synthesized. This particular configuration of the pyrrolidine part was chosen as the starting point because of its stereochemical similarity to natural nucleosides (assuming that the 2' and 4' positions in the pyrrolidine ring are equivalent to the 4' and 1' positions in natural nucleosides, respectively).…”