Inhibitory effect 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 (Rix) could be induced by ascorbic acid (AsA)/Cu(II), a system used for the metal-catalyzed generation of reactive oxygen species. In this study, we observed that this oxidation could be inhibited by high concentrations of mannitol and other sugars and polyols, such as ethylene glycol, glycerol, glucose, and dextran. Similar protective effects with high concentrations of mannitol were also observed in the AsA/CuCl2-induced oxidation of Gly-Met-Gly and Gly-His-Gly. In contrast, (carboxymethyl)cellulose had no protective effect on the metal-catalyzed oxidation of Rix. These results, together with results from deuterium isotope experiments and spectroscopic experiments, suggest that the inhibitory effect of polyols and sugars is probably due to the complexation of transition metal ions rather than a hydroxyl radical scavenging mechanism. However, dextran, a high molecular weight polysaccharide, might function as a hydroxyl radical scavenger to protect Rix from the metal-catalyzed oxidation.
Li
S
S
Department of Pharmaceutical Chemistry, Simons Research Laboratories, University of Kansas, Lawrence 66047, USA.
Patapoff
T W
TW
Nguyen
T H
TH
Borchardt
R T
RT
D001205:Ascorbic Acid / Q000737:chemistry; D002241:Carbohydrates / Q000737:chemistry*; D003300:Copper / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008670:Metals / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D010084:Oxidation-Reduction; D011108:Polymers / Q000737:chemistry*; D012065:Relaxin / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
D002241:Carbohydrates; D008670:Metals; D009842:Oligopeptides; D011108:Polymers; C024617:polyol; D003300:Copper; D012065:Relaxin; C028419:cuprous chloride; D001205:Ascorbic Acid