Inductive Effects on the Energetics of Prolyl Peptide Bond Isomerization: Implications for Collagen Folding and Stability.

摘要: The hydroxylation of proline residues in collagen increases the stability triple helix. Previous X-ray diffraction analyses had demonstrated that presence an electron-withdrawing substituent on pyrrolidine ring has significant structural consequences [Panasik, N., Jr.; Eberhardt, E. S.; Edison, A. Powell, D. R.; Raines, R. T. Int. J. Pept. Protein Res. 1994 , 44, 262−269]. Here, NMR and FTIR spectroscopy were used to ascertain kinetic thermodynamic properties N-acetyl-[β,γ-13C]d,l-proline methyl ester (1); N-acetyl-4(R)-hydroxy-l-proline [13C]methyl (2); N-acetyl-4(R)-fluoro-l-proline (3). pKa's nitrogen atom parent amino acids decrease following order:  (10.8) > 4(R)-hydroxy-l-proline (9.68) 4(R)-fluoro-l-proline (9.23). In water or dioxane, amide I vibrational modes 1 2 3. At 37 °C rate constants for bond isomerization are greater...