Carbon-deuterium vibrational probes of peptide conformation: Alanine dipeptide and glycine dipeptide

The utility of α -carbon deuterium-labeled bonds (C_α -D) as infrared reporters of local peptide conformation was investigated for two model dipeptide compounds: C_α -D labeled alanine dipeptide (Adp- d1) and C_α - D₂ labeled glycine dipeptide (Gdp- d₂). These model compounds adopt structures that are analogous to the motifs found in larger peptides and proteins. For both Adp- d1 and Gdp- d₂, we systematically mapped the entire conformational landscape in the gas phase by optimizing the geometry of the molecule with the values of and ψ, the two dihedral angles that are typically used to characterize the backbone structure of peptides and proteins, held fixed on a uniform grid with 7.5° spacing. Since the conformations were not generally stationary states in the gas phase, we then calculated anharmonic C_α -D and C_α - D₂ stretch transition frequencies for each structure. For Adp- d1 the C_α -D stretch frequency exhibited a maximum variability of 39.4 cm^-1 between the six stable structures identified in the gas phase. The C_α - D₂ frequencies of Gdp- d₂ show an even more substantial difference between its three stable conformations: there is a 40.7 cm^-1 maximum difference in the symmetric C_α - D₂ stretch frequencies and an 81.3 cm^-1 maximum difference in the asymmetric C_α - D₂ stretch frequencies. Moreover, the splitting between the symmetric and asymmetric C_α - D₂ stretch frequencies of Gdp- d₂ is remarkably sensitive to its conformation.