Tuning the Preference of Thiodigalactoside- and Lactosamine-Based Ligands to Galectin-3 over Galectin-1

Summary, in English

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 builder 4-(4-phenoxypheny1)-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.

• Author: Hilde van Hattum; Hilbert M. Branderhorst; Ed E. Moret; Ulf Nilsson; Hakon Leffler; Roland J. Pieters
• Department/s: Centre for Analysis and Synthesis; Division of Microbiology, Immunology and Glycobiology - MIG; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publishing year: 2013
• Language: English
• Pages: 1350-1354
• Publication/Series: Journal of Medicinal Chemistry
• Volume: 56
• Issue: 3
• Links: http://dx.doi.org/10.1021/jm301677r
• Document type: Journal article
• Publisher: The American Chemical Society (ACS)
• Topic: Medicinal Chemistry
• Status: Published
• ISBN/ISSN/Other: ISSN: 1520-4804