Enzyme-Specific Activation versus Leaving Group Ability

Roseri J.A.C. de Beer, Berry Bögels, Gijs Schaftenaar, Barbara Zarzycka, Peter J.L.M. Quaedflieg, Floris L. van Delft, Sander B. Nabuurs, Floris P.J.T. Rutjes*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Enzyme-specific activation and the substrate mimetics strategy are effective ways to circumvent the limited substrate recognition often encountered in protease-catalyzed peptide synthesis. A key structural element in both approaches is the guanidinophenyl (OGp) ester, which enables important interactions for affinity and recognition by the enzyme-at least, this is usually the explanation given for its successful application. In this study we show that leaving group ability is of equal or even greater importance. To this end we used both experimental and computational methods: 1) synthesis of close analogues of OGp, and their evaluation in a dipeptide synthesis assay with trypsin, 2) molecular docking studies to provide insights into the binding mode, and 3) ab initio calculations to evaluate their electronic properties.

Original languageEnglish
Pages (from-to)1785-1790
Number of pages6
Issue number12
Publication statusPublished - 13 Aug 2012
Externally publishedYes


  • Enzyme catalysis
  • Enzyme-specific activation
  • Guanidinophenyl ester
  • Papain
  • Peptides


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