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Monitoring Glycan–Protein Interactions by NMR Spectroscopic Analysis: A Simple Chemical Tag That Mimics Natural CH–π Interactions
Author(s) -
Calle Luis P.,
Echeverria Begoña,
Franconetti Antonio,
Serna Sonia,
FernándezAlonso M. Carmen,
Diercks Tammo,
Cañada F. Javier,
Ardá Ana,
Reichardt NielsChristian,
JiménezBarbero Jesús
Publication year - 2015
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.201501248
Subject(s) - chemistry , acetamide , moiety , glycan , geminal , stereochemistry , molecular recognition , substituent , wheat germ agglutinin , lectin , combinatorial chemistry , molecule , organic chemistry , biochemistry , glycoprotein
Detection of molecular recognition processes requires robust, specific, and easily implementable sensing methods, especially for screening applications. Here, we propose the difluoroacetamide moiety (an acetamide bioisoster) as a novel tag for detecting by NMR analysis those glycan–protein interactions that involve N‐acetylated sugars. Although difluoroacetamide has been used previously as a substituent in medicinal chemistry, here we employ it as a specific sensor to monitor interactions between GlcNAc‐containing glycans and a model lectin (wheat germ agglutinin). In contrast to the widely employed trifluoroacetamide group, the difluoroacetamide tag contains geminal 1 H and 19 F atoms that allow both 1 H and 19 F NMR methods for easy and robust detection of molecular recognition processes involving GlcNAc‐ (or GalNAc‐) moieties over a range of binding affinities. The CHF 2 CONH‐ moiety behaves in a manner that is very similar to that of the natural acetamide fragment in the involved aromatic‐sugar interactions, providing analogous binding energy and conformations, whereas the perfluorinated CF 3 CONH‐ analogue differs more significantly.