Hee Jung

Computational study of conformational preferences of thioamide‐containing azaglycine peptides

The effect of thioamide substitution on the conformational stability of an azaglycine‐containing peptide, For‐AzaGly‐NH2 (1), was investigated for the sake of finding possible applications by using ab initio and DFT methods. As model compounds, For‐[ΨCSNH]‐AzaGly‐NH2 (2), For‐AzaGly‐[ΨCSNH]‐NH2 (3), and For‐[ΨCSNH]‐AzaGly‐[ΨCSNH]‐NH2 (4) were used. Two‐dimensional ϕ‐ψ potential energy surfaces (PESs) for 2–4 were calculated at the B3LYP/6‐31G*//HF/6‐31G* level in gas (ε = 1.0) and in water (ε = 78.4) by applying the isodensity polarizable continuum model (IPCM) method. On the basis of these PESs, the minimum energy conformations for 2–4 were characterized at the B3LYP level with 6‐31G*, 6‐311G**, and 6‐31+G** basis sets. The remarkable structural effect of thioamide substitution for 2–4 is that β‐strand structure is observed as a global or local minimum. The minima of 2–4 are also compared with those for glycine and thioamide‐containing glycine peptides. Our theoretical results demonstrate that compounds 2–4 would be used to design controllable secondary structures.