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Substantial Spatial Flexibility and Hydrogen Bonding within the Catalysis Exerted by Cyclodextrin Artificial Glycosidases
Author(s) -
Bjerre Jeannette,
Bols Mikael
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201000380
Subject(s) - chemistry , catalysis , substrate (aquarium) , stereochemistry , hydrolysis , glycoside hydrolase , artificial enzyme , cyclodextrin , hydrogen bond , carboxylate , enzyme catalysis , combinatorial chemistry , organic chemistry , molecule , oceanography , geology
Herein we report the synthesis of a novel 7 A ,7 D ‐dicyanohydrin‐β‐cyclodextrin that catalyzes the hydrolysis of aryl glycosides with up to 5500 times rate increase ( k cat / k uncat ), functioning as a glycosidase enzyme mimic. For all glycoside substrates tested at 50 m M phosphate buffer this catalysis is superior to previously reported results for 6 A ,6 D ‐dicyanohydrin cyclodextrin (CD) artificial glycosidases, i.e. analogues which have their catalytic group one carbon atom closer to the cyclodextrin cavity. This provides proof of substantial flexibility within the catalysis exerted by these CD chemzymes. A series of permethylated mono‐ and dicyanohydrin α‐ and β‐CDs were also synthesized, and these showed more modest catalytic rate enhancements of up to 110 times (10 % catalysis rate, relative to non‐methylated analogues), implying that the permethylation blocks or hampers catalytically important binding between the saccharide part of the substrate and the CD. For comparison, the permethylated 6 A ,6 D ‐dicarboxylic acid β‐CD was also synthesized and afforded 25 % activity (up to 250 times rate increase) relative to the nonpermethylated 6 A ,6 D ‐dicarboxylic acid β‐CD. This suggests that the catalytic effect of the polar interactions of the ionized carboxylate entity is less dependent on the substrate position. These findings afford new information on the scopes and boundaries for CD artificial glycosidase catalysis, and the spatial flexibility discovered fosters optimism for future advances and discoveries within the field of artificial enzymes.