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ChemMedChem. 2018 Jan 22;13(2):133-137. doi: 10.1002/cmdc.201700744. Epub 2018 Jan 15.

Monosaccharide Derivatives with Low-Nanomolar Lectin Affinity and High Selectivity Based on Combined Fluorine-Amide, Phenyl-Arginine, Sulfur-π, and Halogen Bond Interactions.

Author information

1
Galecto Biotech AB, Sahlgrenska Science Park, Medicinaregatan 8A, 413 46, Gothenburg, Sweden.
2
Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Box 124, 221 00, Lund, Sweden.
3
Red Glead Discovery AB, Medicon Village, 223 63, Lund, Sweden.
4
SARomics Biostructures AB, Medicon Village, 223 63, Lund, Sweden.
5
Biochemistry and Structural Biology, Center for Molecular Protein Science, Department of Chemistry, Lund University, Box 124, 221 00, Lund, Sweden.
6
Department of Laboratory Medicine, Section MIG, Lund University BMC-C1228b, Klinikgatan 28, 221 84, Lund, Sweden.

Abstract

The design of small and high-affinity lectin inhibitors remains a major challenge because the natural ligand binding sites of lectin are often shallow and have polar character. Herein we report that derivatizing galactose with un-natural structural elements that form multiple non-natural lectin-ligand interactions (orthogonal multipolar fluorine-amide, phenyl-arginine, sulfur-π, and halogen bond) can provide inhibitors with extraordinary affinity (low nanomolar) for the model lectin, galectin-3, which is more than five orders of magnitude higher than the parent galactose; moreover, is selective over other galectins.

KEYWORDS:

fluorine multipolar interactions; galectin-3; halogen bonds; inhibitors; lectins; sulfur-π

PMID:
29194992
DOI:
10.1002/cmdc.201700744
[Indexed for MEDLINE]

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