Slate D L, Lee R H, Rodriguez J, Crews P
Institute of Biochemistry and Cell Biology, Syntex Discovery Research, Palo Alto, CA 94304.
Biochem Biophys Res Commun. 1994 Aug 30;203(1):260-4. doi: 10.1006/bbrc.1994.2176.
Halistanol trisulfate, a sulfated steroid derivative, was isolated from the extracts of two different marine sponges (genus Topsentia) by bioassay-guided fractionation. It exhibited an IC50 of approximately 4 microM against pp60v-src, the oncogenic protein tyrosine kinase encoded by Rous sarcoma virus. Removing the sulfate groups by acid hydrolysis produced the inactive tris-alcohol, halistanol. The kinetics of inhibition were examined and revealed that halistanol trisulfate is a competitive inhibitor with respect to the peptide substrate, [val5]-angiotensin II, and a mixed inhibitor with respect to ATP. A number of monosulfated steroids were studied for protein tyrosine kinase inhibitory activity, but were found to be inactive.
三硫酸哈利斯坦醇是一种硫酸化甾体衍生物，通过生物测定导向分级分离法从两种不同的海洋海绵（托普斯提亚属）提取物中分离得到。它对劳氏肉瘤病毒编码的致癌蛋白酪氨酸激酶pp60v-src表现出约4 microM的半数抑制浓度（IC50）。通过酸水解去除硫酸基团可产生无活性的三醇哈利斯坦醇。研究了抑制动力学，结果表明三硫酸哈利斯坦醇对肽底物[缬氨酸5]-血管紧张素II是竞争性抑制剂，对ATP是混合型抑制剂。研究了多种单硫酸化甾体的蛋白酪氨酸激酶抑制活性，但发现它们均无活性。
