Chemical Shifts of Carbonyl Carbons in Peptides and Proteins

We report in this paper the results of an ab initio gauge-including atomic orbital study of the influence of hydrogen-bonding on the carbonyl carbon ( ¹³ Cʹ) chemical shift in peptides and protein model systems. For N-methylacetamide (NMA) interacting with formamide, the experimentally observed trends of the ¹³ Cʹ shielding tensor elements on hydrogen bond distance in peptides are moderately well reproduced. Shielding computations were also performed on SCF-optimized helical and β-turn N-formylpentaalaninamide structures. Here, we find the calculated helix—sheet chemical shift difference to be 4.9 ppm, with the helical site deshielded, in good agreement with experimental trends observed in proteins, where alanine ¹³ Cʹ helical sites are typically deshielded by ~4.6 ppm when compared with sheet or sheetlike residues. The well-known ¹³ Cʹ helix—sheet chemical shift separation is therefore attributable to hydrogen bond formation, since Φ, Ψ effects alone (in model dipeptides) result in small upfield shifts for ¹³ Cʹ in helical sites. Unlike the situation with C ^α , C ^β , N ^H , and ¹⁹ F shielding in proteins, ab initio geometry optimization of hydrogen-bonded systems appears to be essential in order to reproduce experimental shift patterns.