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Open AccessArticle

A Galactoside-Binding Protein Tricked into Binding Unnatural Pyranose Derivatives: 3-Deoxy-3-Methyl-Gulosides Selectively Inhibit Galectin-1

1
Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Box 124, SE-221 00 Lund, Sweden
2
Section MIG, Department of Laboratory Medicine, Lund University, BMC-C1228b, Klinikgatan 28, SE-221 84 Lund, Sweden
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(15), 3786; https://doi.org/10.3390/ijms20153786
Received: 23 June 2019 / Revised: 20 July 2019 / Accepted: 22 July 2019 / Published: 2 August 2019
Galectins are a family of galactoside-recognizing proteins involved in different galectin-subtype-specific inflammatory and tumor-promoting processes, which motivates the development of inhibitors that are more selective galectin inhibitors than natural ligand fragments. Here, we describe the synthesis and evaluation of 3-C-methyl-gulopyranoside derivatives and their evaluation as galectin inhibitors. Methyl 3-deoxy-3-C-(hydroxymethyl)-β-d-gulopyranoside showed 7-fold better affinity for galectin-1 than the natural monosaccharide fragment analog methyl β-d-galactopyranoside, as well as a high selectivity over galectin-2, 3, 4, 7, 8, and 9. Derivatization of the 3-C-hydroxymethyl into amides gave gulosides with improved selectivities and affinities; methyl 3-deoxy-3-C-(methyl-2,3,4,5,6-pentafluorobenzamide)-β-d-gulopyranoside had Kd 700 µM for galectin-1, while not binding any other galectin. View Full-Text
Keywords: galectin-1; gulopyranosides; fluorescence polarization; benzamide; selective galectin-1; gulopyranosides; fluorescence polarization; benzamide; selective
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MDPI and ACS Style

Pal, K.B.; Mahanti, M.; Leffler, H.; Nilsson, U.J. A Galactoside-Binding Protein Tricked into Binding Unnatural Pyranose Derivatives: 3-Deoxy-3-Methyl-Gulosides Selectively Inhibit Galectin-1. Int. J. Mol. Sci. 2019, 20, 3786.

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