Inhibition of prolyl hydroxylase activity and collagen biosynthesis by the anthraquinone glycoside, P-1894B, an inhibitor produced by Streptomyces albogriseolus

P-1894B, a potent prolyl hydroxylase inhibitor produced by Streptomyces albogriseolus subsp. No. 1894, inhibited about 50% of the activity of purified chick embryo prolyl hydroxylase at a concentration of 2.2 x 10(-6) M. The inhibition was noncompetitive with respect to (Pro-Pro-Gly)5 with a Ki of 1.8 x 10(-6)M. When excess amounts of ferrous ions or ascorbate were added to the reaction mixture, the inhibition was slightly reversed. P-1894B at a dose of 0.15 mg/kg reduced the hydroxylation of peptidyl proline and caused a significant inhibition of collagen biosynthesis in the uterus of the immature rat stimulated by the administration of estradiol-17 beta.