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Updated: Jun 3, 2026

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
Solvent Effects on the Energetics of Prolyl Peptide Bond Isomerization
Eric S Eberhardt1, Stewart N Loh, Andrew P Hinck
1Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706.
Abstract:
Racemic Ac-Gly-[β,δ-(13)C]Pro-OMe was synthesized, and the kinetics and thermodynamics of the isomerization of its prolyl peptide bond were determined in nine solvents by using NMR and IR spectroscopy. The free energy of activation is 1.3 kcal/mol larger in water than in aprotic solvents, and correlates with the ability of a solvent to donate a hydrogen bond but not with solvent polarity. These results are consistent with conventional pictures of amide resonance, which require transfer of charge between oxygen and nitrogen during isomerization. Similar medium effects may modulate the stability of planar peptide bonds in the active site of peptidyl-prolyl cis-trans isomerases (PPIases) and during the folding, function, or lysis of proteins.
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