Title：Thiodigalactoside-Bovine Serum Albumin Conjugates as High-Potency Inhibitors of Galectin-3: An Outstanding Example of Multivalent Presentation of Small Molecule Inhibitors

标题： 硫代二半乳糖苷-牛血清白蛋白偶联物作为高活性半乳凝素-3抑制剂：小抑制剂多价展示的一个杰出例子

作者： Zhang H, et al. 

Journal： Bioconjugate Chemistry

发布时间：2018 Apr 18; 29(4): 1266-1275.

Research Background and Objective 

Galectin-3 (Gal-3) is a carbohydrate-binding protein that plays a significant role in various physiological and pathological processes, particularly in cancer, fibrosis, and immune responses. Developing effective inhibitors of Gal-3 is crucial for therapeutic purposes. However, existing Gal-3 inhibitors often suffer from low affinity and specificity. In this study, the authors explore a novel strategy of multivalent presentation using a small molecule inhibitor conjugated to a macromolecular carrier to enhance its binding affinity and inhibition potency.

研究背景与目的

Galectin-3（Gal-3）是一种糖结合蛋白，在多种生理和病理过程中发挥着重要作用，尤其是在肿瘤、纤维化和免疫反应中。开发高效的Gal-3抑制剂对于治疗目的至关重要。然而，现有的Gal-3抑制剂常常存在亲和力和特异性较低的问题。在本研究中，作者探讨了一种创新的多价呈现策略，利用小分子抑制剂与高分子载体的共轭来增强其结合亲和力和抑制效能。

Research Methods 

The researchers synthesized Thiodigalactoside (TDG) and conjugated it with Bovine Serum Albumin (BSA). TDG is a small molecule that specifically binds to Gal-3, while BSA serves as a macromolecular carrier to increase the multivalency of the conjugate, enhancing its inhibitory activity. Several techniques, such as flow cytometry, gel filtration, and surface plasmon resonance (SPR), were used to assess the binding affinity and inhibitory activity of the TDG-BSA conjugates.

研究方法

研究人员合成了**硫代半乳糖苷（TDG）并与牛血清白蛋白（BSA）**共轭。TDG是一种能够特异性结合Gal-3的小分子，而BSA作为高分子载体，能够提高共轭物的多价性，从而增强其抑制活性。研究人员使用流式细胞术、凝胶过滤和表面等离子共振（SPR）等多种技术评估TDG-BSA共轭物对Gal-3的结合亲和力和抑制活性。

Results and Discussion 

The results indicated that the TDG-BSA conjugates exhibited significantly stronger inhibition of Gal-3 compared to the single small molecule TDG. The binding affinity of the conjugates was enhanced, and the inhibitory activity was substantially improved, demonstrating the effectiveness of the multivalent presentation strategy. This approach addresses the limitations of traditional single-molecule inhibitors, such as insufficient affinity and specificity.

结果与讨论

实验结果表明，TDG-BSA共轭物在抑制Gal-3方面显著优于单一的小分子TDG。共轭物的结合亲和力得到增强，抑制活性也得到了显著提高，证明了多价呈现策略的有效性。这一方法有效克服了传统单分子抑制剂在亲和力不足和特异性差方面的局限性。

Conclusion 

This study provides a new strategy for the development of high-potency Gal-3 inhibitors and demonstrates the advantages of using macromolecular carriers for multivalent presentation of small molecule inhibitors. This approach not only enhances the inhibitory effect but also provides a valuable reference for the development of other glycoprotein inhibitors.

结论

这项研究为开发高效的Gal-3抑制剂提供了新的策略，并展示了利用高分子载体实现小分子抑制剂多价呈现的优势。这一方法不仅增强了抑制效果，还为其他糖蛋白抑制剂的开发提供了有价值的参考。

CAS Numbers of Relevant Compounds / 相关化合物的CAS号

1. Bovine Serum Albumin (BSA)
   • CAS Number: 9048-46-8
   • BSA serves as the macromolecular carrier for TDG in the conjugate.
2. Other Potential Galectin-3 Inhibitors
   • Oligosaccharides or galactosides (related small molecules)
     • CAS numbers vary depending on the specific structure of the sugar molecule.