In:
Angewandte Chemie International Edition, Wiley, Vol. 56, No. 25 ( 2017-06-12), p. 7292-7296
Kurzfassung:
DC‐SIGN is a cell‐surface receptor for several pathogenic threats, such as HIV, Ebola virus, or Mycobacterium tuberculosis . Multiple attempts to develop inhibitors of the underlying carbohydrate–protein interactions have been undertaken in the past fifteen years. Still, drug‐like DC‐SIGN ligands are sparse, which is most likely due to its hydrophilic, solvent‐exposed carbohydrate‐binding site. Herein, we report on a parallel fragment screening against DC‐SIGN applying SPR and a reporter displacement assay, which complements previous screenings using 19 F NMR spectroscopy and chemical fragment microarrays. Hit validation by SPR and 1 H– 15 N HSQC NMR spectroscopy revealed that although no fragment bound in the primary carbohydrate site, five secondary sites are available to harbor drug‐like molecules. Building on key interactions of the reported fragment hits, these pockets will be targeted in future approaches to accelerate the development of DC‐SIGN inhibitors.
Materialart:
Online-Ressource
ISSN:
1433-7851
,
1521-3773
DOI:
10.1002/anie.201701943
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2017
ZDB Id:
2011836-3
ZDB Id:
123227-7
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