Hortin G L, Schilling M, Graham J P
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
Biochem Biophys Res Commun. 1988 Jan 15;150(1):342-8. doi: 10.1016/0006-291x(88)90526-8.
Two categories of compounds, substrates of sulfation and sulfate analogs, were tested for the ability to inhibit sulfation of macromolecules secreted by HepG2 cells. Several compounds which most effectively inhibited sulfation without toxic effects on cells were tested for their relative inhibition of sulfation of tyrosine residues (using the fourth component of complement as a model substrate), of N-linked oligosaccharides (alpha 2HS-glycoprotein as substrate), and of proteoglycans. Inhibitors decreased the sulfation of all three classes of substrate, but not always equally. Use of inhibitors from both categories in combination yielded synergistic effects, with more effective inhibition of sulfation and low toxicity. Such combinations of inhibitors should provide a valuable tool for probing the significance of the sulfation of macromolecules.
对两类化合物，即硫酸化底物和硫酸类似物，进行了抑制HepG2细胞分泌的大分子硫酸化能力的测试。对几种能最有效抑制硫酸化且对细胞无毒性作用的化合物，测试了它们对酪氨酸残基（以补体第四成分作为模型底物）、N-连接寡糖（α2HS-糖蛋白作为底物）和蛋白聚糖硫酸化的相对抑制作用。抑制剂降低了所有三类底物的硫酸化，但并非总是同等程度。将两类抑制剂联合使用产生了协同效应，能更有效地抑制硫酸化且毒性较低。这种抑制剂组合应为探究大分子硫酸化的意义提供一个有价值的工具。
