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A Potent Mimetic of the Siglec‐8 Ligand 6’‐Sulfo‐Sialyl Lewis x
Author(s) -
Kroezen Blijke S.,
Conti Gabriele,
Girardi Benedetta,
Cramer Jonathan,
Jiang Xiaohua,
Rabbani Said,
Müller Jennifer,
Kokot Maja,
Luisoni Enrico,
Ricklin Daniel,
Schwardt Oliver,
Ernst Beat
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000649
Subject(s) - sialyl lewis x , pharmacophore , chemistry , ligand (biochemistry) , front cover , virtual screening , glycobiology , siglec , receptor , stereochemistry , biochemistry , computational biology , glycan , biophysics , cover (algebra) , biology , selectin , glycoprotein , organic chemistry , adhesion , mechanical engineering , engineering
The Front Cover shows the interaction of the natural ligand 6′‐sulfo‐sialyl Lewis x and a glycomimetic thereof with Siglec‐8, a cell‐surface receptor considered to be a promising target for the treatment of eosinophil‐ and mast‐cell‐associated diseases such as asthma. Using a combination of pharmacophore analysis, NMR structural information, and chemical modification of the initial hit identified by glycan array screening, Ernst and co‐workers were able to generate a high‐affinity glycomimetic. The elucidation of the structure—activity relationship, accompanied by the analysis of binding thermodynamics and kinetics, sheds light on the underlying binding mechanisms. These results exhibit an important contribution to the further development of the therapeutic potential of Siglec‐8 antagonists. (Cover graphics by Gabriele Conti, Department of Pharmaceutical Sciences, University of Basel.) More information can be found in the Full Paper by Beat Ernst et al.