药用植物果胶与半乳凝素分子互作的选择性及其机制研究

果胶是一类结构复杂的植物多糖，是药用植物的有效成分，具有多种药理活性。半乳凝素是一类能识别β-半乳糖基的凝集素，参与多种生理和病理过程，与多种疾病的发生和发展相关。研究已经表明，果胶能与某些半乳凝素结合，是潜在的半乳凝素抑制剂，但是它们之间作用的选择性及其机制尚不明确。本项目选择40余种结构不同的果胶（涵盖HG、RG-I和RG-II三种主要的结构类型）和三种代表性的半乳凝素，即半乳凝素-1（原型）、-3（嵌合型）、-8（串联重复型），采用多种现代生物学方法，通过分析果胶结构变化对其相互作用亲和力的影响，以及半乳凝素分子中果胶的结合位点/部位，研究果胶与半乳凝素分子相互作用的选择性，从果胶和半乳凝素两方面阐明影响互作的结构因素。研究结果为寻找和开发低毒、高效、选择性好的半乳凝素抑制剂/调节剂提供理论基础，也将对糖生物学的发展起到促进作用。

Pectin, a family of plant polysaccharides with complex structure, possesses multiple pharmacological activities. Pectins are active components of medicinal herbs. Galectin is a family of lectins with conserved carbohydrate recognition domains specific for beta-galactosides. Galectin is involved in multiple physiological and pathological processes, and has been implicated in some diseases. Previous studies show that pectin can bind galectin and is a type of potential galectin inhibitors. However, the selectivity and mechanism remain unclear. Here we address this issue by investigating the selective interaction between pectins and galectins, aiming to provide useful information for developing galectin inhibitors with low toxicity and good selectivity. We will use more than 40 structurally different pectins covering the three main structures (HG, RG-I and RG-II) found in pectin, and three representative galectins - galectin-1 (prototype), galectin-3 (chimera) and galectin-8 (tandem repeat). The selective interaction between pectin and galectin will be investigated with multiple advanced biological methods. Further studies on mechanism will be performed from both pectin and galectin prospects by exploring pectin structures related to binding to each galectin, as well as galectin structural domains relevant to pectin binding. Saccharide-protein interaction is a general topic but poorly understood in the field of glycobiology. This project will certainly provide some new information for better understanding the interaction between polysaccharides and proteins.