INHIBITORY EFFECTS OF SUGARS AND POLYOLS ON THE METAL-CATALYZED OXIDATION OF HUMAN RELAXIN

Previously, our laboratory (Li, S.; et al. Biochemistry 1995, 34, 5762 -5772) showed that the oxidation of recombinant human relaxin (Rlx) co uld be induced by ascorbic acid (AsA)/Cu(II), a system used for the me tal-catalyzed generation of reactive oxygen species. In this study, we observed that this oxidation could be inhibited by high concentration s of mannitol and other sugars and polyols, such as ethylene glycol, g lycerol, glucose, and dextran. Similar protective effects with high co ncentrations of mannitol were also observed in the AsA/CuCl2-induced o xidation of Gly-Met-Gly and Gly-His-Gly. In contrast, (carboxymethyl)c ellulose had no protective effect on the metal-catalyzed oxidation of Rlx. These results, together with results from deuterium isotope exper iments and spectroscopic experiments, suggest that the inhibitory effe ct of polyols and sugars is probably due to the complexation of transi tion metal ions rather than a hydroxyl radical scavenging mechanism. H owever, dextran, a high molecular weight polysaccharide, might functio n as a hydroxyl radical scavenger to protect Rlx from the metal-cataly zed oxidation.