Alberta Ingenuity Centre for Carbohydrate Science, Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
Org Biomol Chem. 2011 May 21;9(10):3658-71. doi: 10.1039/c0ob01089h. Epub 2011 Mar 31.
Structural pre-organization of the multivalent ligands is important for successful interaction with multimeric proteins. Polymer-based heterobifunctional ligands that contain pendant groups prearranged into heterodimers can be used to probe the active site and surrounding area of the receptor. Here we describe the synthesis and activities of a series of galactose conjugates on polyacrylamide and dextran. Conjugation of a second fragment resulted in nanomolar inhibitors of cholera toxin, while the galactose-only progenitors showed no detectable activity.
多价配体的结构预组织对于与多聚体蛋白的成功相互作用很重要。基于聚合物的杂双功能配体，其中包含预先排列成杂二聚体的悬垂基团，可用于探测受体的活性部位和周围区域。在这里，我们描述了一系列半乳糖缀合物在聚丙烯酰胺和葡聚糖上的合成和活性。第二个片段的缀合导致霍乱毒素的纳摩尔抑制剂，而仅半乳糖的前体则没有可检测到的活性。
