Structural optimization of photoswitch ligands for surface attachment of alpha-chymotrypsin and regulation of its surface binding.
A modified gold surface that allows photoregulated binding of alpha-chymotrypsin has previously been reported. Here the development of this surface is reported, through the synthesis of a series of trifluoromethyl ketones and alpha-keto esters containing the azobenzene group and a surface attachment group as photoswitch inhibitors of alpha-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 alpha-chymotrypsin to a degree that could be modulated by UV/Vis irradiation, showing "slow-tight" enzyme binding as observed for inhibitors in solution.
Pearson
David
D
Department of Chemistry and Biochemistry, Ludwig-Maximilian University, 80539 Munich, Germany.
Abell
Andrew D
AD
D001391:Azo Compounds / Q000737:chemistry*; D001665:Binding Sites; D002918:Chymotrypsin / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006046:Gold; D008024:Ligands; D008958:Models, Molecular; D010777:Photochemistry; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013499:Surface Properties
D001391:Azo Compounds; D004791:Enzyme Inhibitors; D008024:Ligands; D011480:Protease Inhibitors; D006046:Gold; D002918:Chymotrypsin; C117608:alpha-chymotrypsin