PT  - JOURNAL ARTICLE
AU  - JEFFREY D. SAFFER
AU  - ROBERT I. GLAZER
TI  - Inhibition of Histone H1 Phosphorylation by Sangivamycin and other Pyrrolopyrimidine Analogues
DP  - 1981 Jul 01
TA  - Molecular Pharmacology
PG  - 211--217
VI  - 20
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/20/1/211.short
4100  - http://molpharm.aspetjournals.org/content/20/1/211.full
SO  - Mol Pharmacol1981 Jul 01; 20
AB  - We have examined the ability of the pyrrolopyrimidine antibiotic, sangivamycin [4-amino-5-carboxamide-7(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine], to inhibit the phosphorylation of the 2% trichloroacetic acid-soluble nuclear proteins from Ehrlich ascites cells in vitro. In whole cells, sangivamycin inhibited histone H1 phosphorylation, with 50% inhibition observed at a drug concentration of 100 µM, but phosphorylation of the high-mobility group (HMG) proteins, HMG 14 and 17, was unaffected. At all concentrations, histone H1 phosphorylation was inhibited to a greater degree than nRNA synthesis. The pyrrolopyrimidine analogues toyocamycin, sangivamycin-amidine, and sangivamycin-amidoxime did not differ substantially from sangivamycin in their inhibitory effects on histone H1 phosphorylation and nRNA synthesis in whole cells, whereas thiosangivamycin was approximately 50-fold more potent. Cell-free assays with partially purified nuclear protein kinase activities, PK-I and PK-II, revealed that sangivamycin was a competitive inhibitor versus ATP with either histone H1 or casein as substrate. The 50% inhibitory concentration of thiosangivamycin for PK-I activity was 40-fold less than sangivamycin and closely paralleled their relative inhibitory activities for inhibiting histone H1 phosphorylation in intact cells in vitro. This relationship was not apparent for sangivamycin-amidine, sangivamycin-amidoxime, and toyocamycin.