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

The utility of α-carbon deuterium-labeled bonds (Cα-D) as infrared reporters of local peptide conformation was investigated for two model dipeptide compounds: Cα-D labeled alanine dipeptide (Adp-d₁) and Cα-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 φ 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 Cα-D and Cα-D2 stretch transition frequencies for each structure. For Adp-d₁ the Cα-D stretch frequency exhibited a maximum variability of 39.4 cm^-1 between the six stable structures identified in the gas phase. The Cα-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 Cα-D2 stretch frequencies and an 81.3 cm^-1 maximum difference in the asymmetric Cα-D2 stretch frequencies. Moreover, the splitting between the symmetric and asymmetric Cα-D2 stretch frequencies of Gdp-d₂ is remarkably sensitive to its conformation.