Local interactions in peptides

We report the results of a joint NMR and theoretical investigation devoted to the conformational properties of N-acetyl-N′-methylamides of aliphatic amino acids with side chains of increasing bulkiness: Gly, Ala, Leu, Ile, and tert. Leu. In this series, determination of the coupling constants ³J_HNCαH together with the coupling constants ³J_C′NCαH (thanks to specific carbon-13 labeling of the N-acetyl carbonyl group) led to the derivation of alternative A, B, and C parameters in a Karplus-type relation expressing the dependence of ³J_C′NCαH upon the φ dihedral angle. The value of the latter is found to increase regularly following the increase of the side-chain bulkiness. The theoretical conformational analysis is performed by applying the SIBFA procedure, which uses empirical formulas based on ab initio SCF computations. The conformational energy maps illustrate the progressive distortion of the backbone conformation incurred in the series Gly to tert.Leu. Theoretical values computed for ³J_HNCαH and ³J_C′NCαH are found to be in a good quantitative agreement with the experimental ones.