Isotope effects on chemical shifts of proteins and peptides

Isotope effects on chemical shifts, nΔ 13C(D), nΔ 1H(D), 1Δ 15N(D) and 1Δ 13C(18O), and solvent isotope effects in proteins are reviewed and references are provided to related cases. The isotope effects included are motivated by the effects occurring in perdeuterated proteins and effects of 13C and 15N labelling combined with effects of an H2O– D2O mixture. The focus is on structural information. The following isotope effects depend on structure: 1Δ 15N(D), 1Δ 13C(D), 2Δ 13C–α(ND), 3Δ 13C–α(ND) and 3Δ 13C–β(ND). Equilibrium isotope effects on chemical shifts are briefly discussed by the elegant use of 1Δ 13C(18O) and 1Δ 13C(15N) in the determination of pKa values. Ab initio calculations of isotope effects show promise both in traditional cases and for describing the new type of isotope effects observed in paramagnetic proteins.