Tuning the Preference of Thiodigalactoside- and Lactosamine-Based Ligands to Galectin-3 over Galectin-1
| Autor: | Ed E. Moret, Hilbert M. Branderhorst, Hilde van Hattum, Ulf J. Nilsson, Roland J. Pieters, Hakon Leffler |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Galectin 1
Stereochemistry Galectin 3 Substituent Ligands 01 natural sciences Mass Spectrometry Thiogalactosides 03 medical and health sciences chemistry.chemical_compound Drug Discovery Derivatization 030304 developmental biology 0303 health sciences Molecular Structure 010405 organic chemistry Chemistry Amino Sugars 0104 chemical sciences 3. Good health Galectin-3 Galactose Galectin-1 Molecular Medicine Selectivity |
| Zdroj: | Journal of Medicinal Chemistry; Vol 56 |
| ISSN: | 0022-2623 |
| DOI: | 10.1021/jm301677r |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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