Abstract
Fucosylation patterns in cell‐surface glycans are essential mediators of recognition and signalling. Aberrations in these signatures serve as vital diagnostic markers of disease progression, and so understanding fucose‐protein interactions at the molecular level is crucial. Molecular editing of l‐fucose (Fuc) at C2 with fluorine provides a platform to reconcile the ubiquity of fucosylation with the paucity of strategies to interrogate site‐specific interactions. Through judicious introduction of a pseudo‐equatorial fluorine [C(sp3)‐F] adjacent to the anomeric position, β‐selective fucosylation can be achieved with a range of diverse acceptors (>50:1): the selectivity of this process can be inverted through changes in the donor scaffold. Reaction development was driven by the desire to construct a fluorinated analogue of Lewis antigen a (F‐Lea), in which fluorine replaces a key OH group at C2. Lea is a ligand for Lectin B (LecB) in the pathogen Pseudomonas aeruginosa and thus delineating the importance of key interactions in this complex has ramifications for drug discovery. Independent syntheses of Lea and F‐Lea, and systematic bioNMR analyses with both glycans has unequivocally established the essential role of O2 of fucose in the Lea‐LecB complex.
Published Version
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