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Papain‐Specific Activating Esters in Aqueous Dipeptide Synthesis
Author(s) -
de Beer Roseri J. A. C.,
Zarzycka Barbara,
Mariman Michiel,
AmatdjaisGroenen Helene I. V.,
Mulders Marc J.,
Quaedflieg Peter J. L. M.,
van Delft Floris L.,
Nabuurs Sander B.,
Rutjes Floris P. J. T.
Publication year - 2012
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201200017
Subject(s) - dipeptide , chemistry , peptide synthesis , peptide , combinatorial chemistry , amino acid , hydrolysis , chemical synthesis , papain , peptide bond , aqueous solution , enzyme , organic chemistry , stereochemistry , biochemistry , in vitro
Enzymatic peptide synthesis has the potential to be a viable alternative for chemical peptide synthesis. Because of the increasing commercial interest in peptides, new and improved enzymatic synthesis methods are desirable. In recently developed enzymatic strategies such as substrate mimetic approaches and enzyme‐specific activation, use of the guanidinophenyl ester (OGp) group has been shown to suffer from some drawbacks. OGp esters are sensitive to spontaneous chemical hydrolysis and the group is expensive to synthesize and therefore not suitable for large‐scale applications. On the basis of earlier computational studies, we hypothesized that OGp might be replaceable by simpler ester groups to make the enzyme‐specific activation approach to peptide bond formation more accessible. To this end, a set of potential activating esters (Z‐Gly‐Act) was designed, synthesized, and evaluated. Both the benzyl (OBn) and the dimethylaminophenyl (ODmap) esters gave promising results. For these esters, the scope of a model dipeptide synthesis reaction under aqueous conditions was investigated by varying the amino acid donor. The results were compared with those obtained from a previous study of Z‐X AA ‐OGp esters. Computational docking analysis of the set of esters was performed in order to provide insight into the differences in the reactivities of all the potential activating esters. Finally, selected ODmap‐ and OBn‐activated amino acids were applied in the synthesis of two biologically active dipeptides on preparative scales.