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Structural Optimization of Photoswitch Ligands for Surface Attachment of α‐Chymotrypsin and Regulation of Its Surface Binding
Author(s) -
Pearson David,
Abell Andrew D.
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200903369
Subject(s) - photoisomerization , azobenzene , photoswitch , chemistry , chymotrypsin , trifluoromethyl , photochemistry , stereochemistry , trypsin , combinatorial chemistry , enzyme , organic chemistry , isomerization , catalysis , molecule , alkyl
A modified gold surface that allows photoregulated binding of α‐chymotrypsin has previously been reported. Here the development of this surface is reported, through the synthesis of a series of trifluoromethyl ketones and α‐keto esters containing the azobenzene group and a surface attachment group as photoswitch inhibitors of α‐chymotrypsin. All of the compounds are inhibitors of the enzyme, with activity that can be modulated by photoisomerization. The best photoswitch shows a reversible change in IC 50 inhibition constant of >5.3 times on photoisomerization. The trifluoromethyl ketone 1 exhibited excellent photoswitching and was attached to a gold surface in a two‐step procedure involving an azide–alkyne cycloaddition. The resulting modified surface bound α‐chymotrypsin to a degree that could be modulated by UV/Vis irradiation, showing “slow‐tight” enzyme binding as observed for inhibitors in solution.