Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Proteomics. 2010 May;10(10):1946-53. doi: 10.1002/pmic.200900581.
Human galectin-3 (hGal-3) is a mammalian lectin involved in regulation of RNA splicing, apoptosis, cell differentiation, and proliferation. Multimerized extracellular hGal-3 is thought to crosslink cells by binding to glycoproteins and glycosylated cancer antigens on the cell surface or extracellular matrix. Fluorescence spectroscopy and circular dichroism were used to study the interaction of hGal-3 with two anticancer agents: bohemine and Zn porphyrin (ZnTPPS(4)). The dissociation constant (k(D)) for binding of bohemine with hGal-3 was k(D) 0.23+/-0.05 microM. The hyperbolic titration curve indicated the presence of a single bohemine binding site. The binding of ZnTPPS(4) to hGal-3 (with and without lactose) is of high affinity having k(D)=0.18-0.20 microM and is not inhibited by lactose, indicating that ZnTPPS(4) and carbohydrate bind different sites. Circular dichroism spectra of the hGal-3 complexes suggested that the binding of the hydrophobic compounds changed the hGal-3 secondary structure. In summary, we show that two compounds with anticancer activity, bohemine and ZnTPPS(4), have high affinity for hGal-3 at a site that is distinct from its carbohydrate site. Since hGal-3 binds to several carbohydrate cancer antigens, the results suggest that it may have utility in the targeted delivery of drugs for cancer.
人半乳糖凝集素-3（hGal-3）是一种参与调节 RNA 剪接、细胞凋亡、细胞分化和增殖的哺乳动物凝集素。多聚化的细胞外 hGal-3 被认为通过与细胞表面或细胞外基质上的糖蛋白和糖基化的癌症抗原结合来交联细胞。荧光光谱和圆二色性用于研究 hGal-3 与两种抗癌剂：甜菜碱和 Zn 卟啉（ZnTPPS（4））的相互作用。甜菜碱与 hGal-3 结合的离解常数（k(D)）为 k(D) 0.23+/-0.05 microM。双曲线滴定曲线表明存在一个单一的甜菜碱结合位点。ZnTPPS（4）与 hGal-3（有和没有乳糖）的结合具有高亲和力，k(D)=0.18-0.20 microM，并且不受乳糖抑制，表明 ZnTPPS（4）和碳水化合物结合不同的位点。hGal-3 复合物的圆二色性光谱表明，疏水性化合物的结合改变了 hGal-3 的二级结构。总之，我们表明，两种具有抗癌活性的化合物，甜菜碱和 ZnTPPS（4），在与碳水化合物结合位点不同的位点上对 hGal-3 具有高亲和力。由于 hGal-3 与几种碳水化合物癌症抗原结合，结果表明它可能在癌症药物的靶向递送上具有实用性。
