The design of small and high‐affinity lectin inhibitors remains a major challenge because the natural ligand binding sites of lectin are often shallow and have polar character. Herein we report that derivatizing galactose with un‐natural structural elements that form multiple non‐natural lectin–ligand interactions (orthogonal multipolar fluorine–amide, phenyl–arginine, sulfur–π, and halogen bond) can provide inhibitors with extraordinary affinity (low nanomolar) for the model lectin, galectin‐3, which is more than five orders of magnitude higher than the parent galactose; moreover, is selective over other galectins.

中文翻译：

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基于氟-酰胺，苯基-精氨酸，硫-π和卤素键相互作用的低纳摩尔凝集素亲和力和高选择性的单糖衍生物

小和高亲和力的凝集素抑制剂的设计仍然是一个重大挑战，因为凝集素的天然配体结合位点通常很浅并且具有极性。在此我们报告说，用形成多种非天然凝集素-配体相互作用的非天然结构元素（正交多极性氟-酰胺，苯基-精氨酸，硫-π和卤素键）衍生化半乳糖可以为抑制剂提供非凡的亲和力（低纳摩尔浓度） ）对于模型凝集素galectin-3，比亲代半乳糖高出五个数量级; 而且，对其他半乳糖凝集素具有选择性。