Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Box 124, SE-221 00 Lund, Sweden.
Section MIG, Department of Laboratory Medicine, Lund University, BMC-C1228b, Klinikgatan 28, SE-221 84 Lund, Sweden.
Int J Mol Sci. 2019 Aug 2;20(15):3786. doi: 10.3390/ijms20153786.
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--methyl-gulopyranoside derivatives and their evaluation as galectin inhibitors. Methyl 3-deoxy-3--(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--hydroxymethyl into amides gave gulosides with improved selectivities and affinities; methyl 3-deoxy-3--(methyl-2,3,4,5,6-pentafluorobenzamide)-β-d-gulopyranoside had K 700 µM for galectin-1, while not binding any other galectin.
半乳凝集素是一类能识别半乳糖的蛋白，参与多种半乳糖凝集素亚型特异性的炎症和肿瘤促进过程，这促使人们开发出比天然配体片段更具选择性的半乳糖凝集素抑制剂。在这里，我们描述了 3--甲基-吡喃葡萄糖苷衍生物的合成和评估及其作为半乳糖凝集素抑制剂的评估。3-脱氧-3--(羟甲基)-β-d-吡喃葡萄糖苷对半乳糖凝集素-1的亲和力比天然单糖片段类似物甲基-β-d-吡喃半乳糖苷高 7 倍，对半乳糖凝集素-2、3、4、7、8 和 9 具有很高的选择性。将 3--羟甲基衍生化为酰胺，得到了具有改善的选择性和亲和力的糖苷；甲基 3-脱氧-3--(甲基-2,3,4,5,6-五氟苯甲酰胺)-β-d-吡喃葡萄糖苷对半乳糖凝集素-1 的 K i 为 700µM，而不与任何其他半乳糖凝集素结合。
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