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Updated: Feb 4, 2026

Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library
Published on: June 20, 2014
Enzymatic Hydrolysis of Tertiary Amide Bonds by anti Nucleophilic Attack and Protonation
1School of Engineering Sciences in Chemistry, Biotechnology and Health, Science for Life Laboratory, Department of Fibre and Polymer Technology, and Department of Protein Science , KTH Royal Institute of Technology , Solna , Sweden 17165.
Abstract:
The molecular mechanisms conferring high resistance of planar tertiary amide bonds to hydrolysis by most enzymes have remained elusive. To provide a chemical explanation to this unresolved puzzle, UB3LYP calculations were performed on an active site model of Xaa-Pro peptidases. The calculated reaction mechanism demonstrates that biocatalysts capable of tertiary amide bond hydrolysis capitalize on anti nucleophilic attack and protonation of the amide nitrogen, in contrast to the traditional syn displayed by amidases and proteases acting on secondary amide bonds.
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