Tuning the preference of thiodigalactoside- and lactosamine-based ligands to galectin-3 over galectin-1.

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van Hattum H, Branderhorst HM, Moret EE, Nilsson UJ, Leffler H, Pieters RJ

Tuning the preference of thiodigalactoside- and lactosamine-based ligands to galectin-3 over galectin-1.

J Med Chem. 2013 Feb 14;56(3):1350-4. doi: 10.1021/jm301677r. Epub 2013 Jan 23.

PubMed ID

23281927 [ View in PubMed

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Abstract

Inhibitors for galectin-1 and -3 were synthesized from thiodigalactoside and lactosamine by derivatization of the galactose C3. Introduction of 4-phenyl-1H-1,2,3-triazol-1-yl substituents at the thiodigalactoside C3 by CuAAC, targeting arginine-arene interactions, increased the affinity to 13 nM but yielded little selectivity. The bulkier 4-(4-phenoxyphenyl)-1H-1,2,3-triazol-1-yl substituent, however, increased the preference for galectin-3 over galectin-1 to more than 200-fold. Modeling showed more arginine-arene interactions for galectin-3 than for galectin-1. Introducing 4-phenoxyaryl groups on lactosamine had a similar effect.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Thiodigalactoside	Galectin-1	Kd (nM)	24000	N/A	N/A	Details