The drugs-protein binding study is of growing importance for drug-repurposing against amyloidosis. In this work, we study the binding of teicoplanin (TPN), a glycopeptide antibiotic, with bovine serum albumin (BSA) in its neutral (N), physiological (P) and basic (B) forms, which exist at pH 6, pH 7.4 and pH 9, respectively. The binding and thermodynamic parameters of TPN binding were determined by isothermal titration calorimetry (ITC) and fluorescence quench titration methods. Two binding sites were observed for N and P forms, whereas B form showed only one binding site. ITC and molecular docking results indicated that TPN-BSA complex formation is stabilized by hydrogen bonds, salt bridges and hydrophobic interaction. The red-edge excitation shift (REES) study indicated an ordered compact and spatial arrangement of the TPN bound protein molecule. TPN was found to affect the secondary and tertiary structures of B form only. The TPN binding was observed to marginally stabilize BSA isomers. TPN was also found to inhibit BSA aggregation as monitored by Rayleigh light scattering and thioflavin T binding assay. The current in vitro study will open a new path to explore the possible use of TPN as potential drugs to treat amyloidosis.

药物-蛋白质结合研究对于针对淀粉样变性的药物再利用越来越重要。在这项工作中，我们研究了糖肽抗生素替考拉宁（TPN）与牛血清白蛋白（BSA）的中性（N），生理（P）和碱性（B）形式的结合，pH 6，pH分别为7.4和pH 9。TPN结合的结合和热力学参数通过等温滴定热法（ITC）和荧光猝灭滴定法确定。对于N和P形式观察到两个结合位点，而B形式仅显示一个结合位点。ITC和分子对接结果表明，TPN-BSA复合物的形成通过氢键，盐桥和疏水相互作用而稳定。红边激发位移（REES）研究表明TPN结合蛋白分子的有序紧凑和空间排列。发现TPN仅影响B形式的二级和三级结构。观察到TPN结合可略微稳定BSA异构体。如通过瑞利光散射和硫黄素T结合测定所监测的，还发现TPN抑制BSA聚集。目前体外研究将为探索将TPN用作治疗淀粉样变性病的潜在药物开辟新的途径。