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Synthetic Receptors for the High‐Affinity Recognition of O‐GlcNAc Derivatives
Author(s) -
Rios Pablo,
Carter Tom S.,
Mooibroek Tiddo J.,
Crump Matthew P.,
Lisbjerg Micke,
Pittelkow Michael,
Supekar Nitin T.,
Boons GeertJan,
Davis Anthony P.
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201510611
Subject(s) - receptor , affinities , chemistry , peptide , alkoxy group , stereochemistry , carbohydrate , aqueous solution , glycoside , biochemistry , combinatorial chemistry , organic chemistry , alkyl
The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water‐soluble carbohydrate receptors (“synthetic lectins”). Both systems show outstanding affinities for derivatives of N ‐acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc‐β‐OMe with K a ≈20 000 m −1 , whereas the other one binds an O‐GlcNAcylated peptide with K a ≈70 000 m −1 . These values substantially exceed those usually measured for GlcNAc‐binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl–peptide complex can be explained by extra‐cavity interactions, raising the possibility of a family of complementary receptors for O‐GlcNAc in different contexts.