Synthetic Receptors for the High-Affinity Recognition of O-GlcNAc Derivatives
Citation
Rios, P, Carter, TS, Mooibroek, T, Crump, M, Lisbjerg, M, Pittelkow, M, Supekar, NT, Boons, G-J & Davis, AP, 2016, ‘Synthetic Receptors for the High-Affinity Recognition of O-GlcNAc Derivatives’. Angewandte Chemie International Edition, vol 55., pp. 3387?3392
Abstract
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 Ka≈20 000 m−1, whereas the other one binds an O-GlcNAcylated peptide with Ka≈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.
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