Stereochemistry of polypeptoid chain configurations

Abstract

Like polypeptides, peptoids, or N‐substituted glycine oligomers, have intrinsic conformational preferences due to their amide backbones and close spacing of side chain substituents. However, the conformations that peptoids adopt are distinct from polypeptides due to several structural differences: the peptoid backbone is composed of tertiary amide bonds that have trans and cis conformers similar in energy, they lack a backbone hydrogen bond donor, and have an N‐substituent. To better understand how these differences manifest in actual peptoid structures, we analyzed 46 high quality, experimentally determined peptoid structures reported in the literature to extract their backbone conformational preferences. One hundred thirty‐two monomer dihedral angle pairs were compared to the calculated energy landscape for the peptoid Ramachandran plot, and were found to fall within the expected minima. Interestingly, only two regions of the backbone dihedral angles ϕ and ψ were found to be populated that are mirror images of each other. Furthermore, these two conformers are present in both cis and trans forms. Thus, there are four primary conformers that are sufficient to describe almost all known backbone conformations for peptoid oligomers, despite conformational constraints imposed by a variety of side chains, macrocyclization, or crystal packing forces. Because these conformers are predominant in peptoid structure, and are distinct from those found in protein secondary structures, we propose a simple naming system to aid in the description and classification of peptoid structure.

Atomic-level engineering and imaging of polypeptoid crystal lattices

“…Initial coordinates for MD simulations were generated with all backbones in the cis -amide conformation as suggested in recent studies (18, 21). The backbone Φ and Ψ angles of the Cα alternated between Z Rc (∼90, ∼150) and Z Sc (∼−90, ∼−150) (22). Peptoid chains were arranged in blocks of 12 stacked parallel in the a dimension, with these blocks arranged ether parallel or antiparallel to one another in the c dimension to form a periodic monolayer configuration.…”

Unconstrained peptoid tetramer exhibits a predominant conformation in aqueous solution

“…Interestingly, the spread in dihedral angles was very narrow for both of these residues, and they populate the known energy minima of the Ac‐Sar‐Sar‐N(Me) 2 Ramachandran plot . Specifically, residue 2 and residue 3 occupy the Z Rt and Z Sc conformations, respectively …”

The Challenge of Conformational Isomerism in Cyclic Peptoids

“…A recent analysis of torsion angles reported in high‐resolution peptoid structures revealed that the majority of the recorded ϕ and ψ dihedral angles are clustered in confined spaces of the Ramachandran plot that are mirror images of one another (ϕ ≈ 70°, ψ ≈ 180°, and ϕ ≈ –70°, ψ ≈ 180°), independently from the cis or trans amide bonds geometry of the oligomeric species (Figure A). Interestingly, similar values for ϕ and ψ torsion angles have also been found in polyproline type I (PPI, ϕ ≈ –75°, ψ ≈ 160°) and type II (PPII, ϕ ≈ –75°, ψ ≈ 145°) helices (both showing amide bonds with p S planar chirality).…”