Tryptophan Chemical Shift in Peptides and Proteins:  A Solid State Carbon-13 Nuclear Magnetic Resonance Spectroscopic and Quantum Chemical Investigation

We have obtained the carbon-13 nuclear magnetic resonance spectra of a series of tryptophan-containing peptides and model systems, together with their X-ray crystallographic structures, and used quantum chemical methods to predict the 13C NMR shifts (or shieldings) of all nonprotonated aromatic carbons (Cγ, Cδ 2 , and Cε 2 ). Overall, there is generally good accord between theory and experiment. The chemical shifts of Trp Cγ in several proteins, hen egg white lysozyme, horse myoglobin, horse heart cytochrome c, and four carbonmonoxyhemoglobins, are also well predicted. The overall Trp Cγ shift range seen in the peptides and proteins is 11.4 ppm, and individual shifts (or shieldings) are predicted with an rms error of ∼1.4 ppm (R value = 0.86). Unlike Cα and NH chemical shifts, which are primarily a function of the backbone φ,ψ torsion angles, the Trp Cγ shifts are shown to be correlated with the side-chain torsion angles χ1 and χ2 and appear to arise, at least in part, from γ-gauche interactions with the backbone C‘ and NH atoms. This work helps solve the problem of the chemical shift nonequivalences of nonprotonated aromatic carbons in proteins first identified over 30 years ago and opens up the possibility of using aromatic carbon chemical shift information in structure determination.