The marine natural product, halistanol trisulfate, inhibits pp60v-src protein tyrosine kinase activity.
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.
Slate
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DL
Institute of Biochemistry and Cell Biology, Syntex Discovery Research, Palo Alto, CA 94304.
Lee
R H
RH
Rodriguez
J
J
Crews
P
P
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000201:enzymology / Q000235:genetics; D002461:Cell Line, Transformed; D007700:Kinetics; D015394:Molecular Structure; D015688:Oncogene Protein pp60(v-src) / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000302:isolation & purification; D011161:Porifera; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D013261:Sterols / Q000302:isolation & purification / Q000494:pharmacology*
D013261:Sterols; C072244:halistanol trisulfate; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)