Search of ligands for the amyloidogenic protein beta2-microglobulin by capillary electrophoresis and other techniques

Beta2-microglobulin (beta2-m) is a small amyloidogenic protein normally present on the surface of most nucleated cells and responsible for dialysis-related amyloidosis, which represents a severe complication of long-term hemodialysis. A therapeutic approach for this amyloidosis could be based on the stabilization of beta2-m through the binding to a small molecule, and consequent inhibition of protein misfolding and amyloid fibril formation. A few compounds have been described to weakly bind beta2-m, including the drug suramin. The lack of a binding site for nonpolypeptidic ligands on the beta2-m structure makes it difficult for both the identification of functional groups responsible for the binding and the search of hits to be optimized. The characterization of the binding properties of suramin for beta2-m by using three different techniques (surface plasmon resonance, affinity CE (ACE), ultrafiltration) is here described and the results obtained are compared. The common features of the chemical structures of the compounds known to bind the protein led us to select 200 sulfonated/suramin-like molecules from a wider chemical library on the basis of similarity rules, so as to possibly single out some interesting hits and to gain more information on the functional groups involved in the binding. The development of screening methods to test the compounds by using ultrafiltration and ACE is described.     

基于表面等离子体子共振成像技术研究苏拉明和顺铂对肝癌细胞生长的抑制作用简

基于表面等离子体子共振成像(SPRi)技术提出了一种实时、非标记的新型抗癌药物药效评估方法. 以聚二甲基硅氧烷(PDMS)为材料,制作了包含微柱结构的微流控芯片作为流通反应池,配合自行设计组装的SPRi生物传感器完成肿瘤细胞的特异性捕获及检测,研究了苏拉明和顺铂对肝癌细胞HepG2的生长抑制作用. 同时引入辅助验证实验,即采用常规八肽胆囊收缩素(简称CCK-8)法测定上述药物对肝癌细胞增殖的抑制作用. SPRi检测结果表明,苏拉明和顺铂能抑制肿瘤细胞HepG2增殖并呈现剂量、时间依赖关系.     

基于表面等离子体子共振成像技术研究苏拉明和顺铂对肝癌细胞生长的抑制作用

基于表面等离子体子共振成像(SPRi)技术提出了一种实时、 非标记的新型抗癌药物药效评估方法. 以聚二甲基硅氧烷(PDMS)为材料, 制作了包含微柱结构的微流控芯片作为流通反应池, 配合自行设计组装的SPRi生物传感器完成肿瘤细胞的特异性捕获及检测, 研究了苏拉明和顺铂对肝癌细胞HepG2的生长抑制作用. 同时引入辅助验证实验, 即采用常规八肽胆囊收缩素(简称CCK-8)法测定上述药物对肝癌细胞增殖的抑制作用. SPRi检测结果表明, 苏拉明和顺铂能抑制肿瘤细胞HepG2增殖并呈现剂量、 时间依赖关系.     

An ‘inside-out’ approach to suramin analogues

An approach to the synthesis of suramin analogues has been realised, which avoids synthetic problems associated with conventional routes. The use of isobutyl ester protecting groups for sulfonic acids was crucial to the success of the strategy, because these were able to be cleanly deprotected with sodium iodide, yielding the sodium salts of the corresponding sulfonic acids.