Factors affecting conformation in proline-containing peptides

NMR was used to study the thermodynamics of the cis --> trans isomerization for prolyl amide bonds in the compounds shown. The magnitude of K-t/c, for C-terminal esters is greater than for the corresponding amides, signifying stronger backbone stereoelectronic effects in esters. Increasing the steric bulk of the N-terminal residue from Ac- to Ac-Gly- favors the trans conformation. Incorporation of a Phe residue N-terminal to Pro, however, shifts the equilibrium in favor of the cis conformation, via a stabilizing aromatic-proline interaction.