Chiroptical labeling of folded polypeptide conformations: The thioamide probe

This paper reports the chiroptical properties of thionated N‐acyl amino acid and N‐acyl dipeptide N′‐methylamide models. It was found that the optical activity of the thioamide chromophore is dominated by the chiral contribution of perturbants attached to C α at the N‐H side of the thioamide group. The appearance of a strong negative ππ* band near 270 nm is indicative of the semiextended conformation of this residue. The ϕ ∼ −70°, ψ ⩾ 120° set of torsion angles is compatible with a type II β t ‐turn or a γ t ‐turn conformation with the perturbing N‐H side residue in the i + 1 position of the turn. (The subscript t or tt denotes that one or both of the H‐bonded moieties is thioamide.) Earlier data show that both β t ‐ and γ t ‐turns may be fixed by CS ⃛H‐N(CO) intramolecular H bonds. The appearance of one or two weak n π* bands and a positive ππ* band at about 270 nm is characteristic of type II β t ‐turns containing the H‐bonded thioamide group attached to the glycine residue in position i + 2. The extended conformation (ϕ ∼ −140°, ψ ∼ 140°) of a residue after the thioamide group gives rise to a negative n π* and a positive ππ* band of comparable magnitude. Peptid1e sequences with alternating thioamide–amide–thioamide backbone tend to adopt 1 t ⇆ 4 t H‐bonded β tt conformations. CD studies show that type II β tt ‐turns have unique chiroptical properties: the ππ* region is dominated by an exceedingly strong negative band near 260 nm (|Δε| = 19–24) accompanied by a weaker band at higher wavelength values.