Ab initio MO Theory – An Important Tool in Foldamer Research: Prediction of Helices in Oligomers of ω‐Amino Acids

Abstract

The enormous developments of computer technologies allow the broad employment of ab initio MO theory in foldamer research. In this review, we demonstrate the efficiency and reliability of ab initio MO methods for the description of the helix formation in oligomers of ω‐amino acids on the basis of representative examples. Thus, ab initio MO theory successfully accompanies foldamer research by confirmation and interpretation of experimental results and stimulation of future experiments. The high predictive power of the methods opens the way to novel structure classes with special properties. Nowadays, ab initio MO theory has become an inherent part in the arsenal of methods applied in foldamer research.

β- and γ-Amino Acids at α-Helical Interfaces: Toward the Formation of Highly Stable Foldameric Coiled Coils

“…In Acid-HCAN, polar histidine occupies the hydrophobic core position a′ 15 . However, similar to our previous result obtained in a parallel regime, 20 cysteine is found in the remaining hydrophobic core position d′ 18 . The presence of another polar residue at position g′ 21 in combination with the rather small hydrophobic alanine at position e′ 19 indicates that this assembly is stabilized by electrostatic interactions rather than being a consequence of the hydrophobic effect.…”

“…We assumed that the C-terminal immobilization of B3β2γ would lead to the isolation of different and perhaps even more thermally stable complexes based on noncovalent interactions under an antiparallel coiled coil regime. Therefore, B3β2γ was immobilized on streptavidin coated magnetic particles via a Cterminally attached biotin and the four central heptad positions of the Acid-pp α-peptide that directly interact with the βγ-segment of the chimeric B3β2γ peptide (a' 15 , d′ 18 , e′ 19 , and g′ 21 ) were randomized. After six rounds of panning, four sequences were isolated (Figure 1).…”

Modulating the Structural Properties of α,γ‐Hybrid Peptides by α‐Amino Acid Residues: Uniform 12‐Helix Versus “Mixed” 12/10‐Helix

“…The torsion angles for the Aic residues are φ =−56±6°, θ 1 =−56±6°, θ 2 =143±16°, and ψ =−115±8°. These torsion angles also differ from those in the corresponding 12‐helix alternatives –,–,. The torsion angle θ 2 of the Aic residues corresponds to an extended conformation, whereas gauche conformations occur in the 12/10‐helix and the 12‐helix alternative.…”

Conformational properties and aggregation of homo‐oligomeric β3(R)‐valine peptides in organic solvents

“…The heightened interest in the conformations of β‐ and γ‐ peptides in recent years has been stimulated by the recognition that intramolecular hydrogen‐bonded structures, unobserved in α‐ peptide sequences, are readily adopted in homo‐oligomeric sequences of these backbone expanded amino acid residues . In particular, the 14‐helical structures established for β‐oligopeptides provide a dramatic example of the inversion of hydrogen bond direction in peptide helices .…”