[Effect of IH764-3 on prolyl hydroxylation in collagen biosynthesis].

Previous study showed that IH764-3 selectively inhibited the synthesis and secretion of collagen, suggesting that the effect of the drug might be due to inhibition of prolyl hydroxylation. In this paper, we report the effect of IH764-3 on prolyl hydroxylation in collagen biosynthesis. Our results showed that the protocollagen substrate (Pro-Pro-Gly)10 9H2O of prolyl hydroxylation by proline hydroxylase isolated from 13-day-old chick embryos in the presence of a-ketoglutarate, ascorbic acid and Fe2+ was inhibited by IH764-3. The inhibition rate was about 50% at a concentration of 0.24 mmol/L. Further investigation demonstrated that IH764-3 did not bind to prolyl hydroxylase, and the inhibition of enzymatic prolyl hydroxylation was found to be due to chelation of the Fe2+ required for the enzymatic reaction. The molar ratio of Fe2+ to IH764-3 (1:3) was determined by the equilibrium movement method, and the chelate was postulated to be a octahedral complex.