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Pyridoxamine protects protein backbone from oxidative fragmentation
Authors:Sergei Chetyrkin  Missy Mathis  W. Hayes McDonald  Xavier Shackelford  Billy Hudson  Paul Voziyan
Affiliation:aDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA;bDepartment of Biochemistry, Vanderbilt University Medical Center, Nashville, TN 37232, USA;cDepartment of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Abstract:Oxidative damage to proteins is one of the major pathogenic mechanisms in many chronic diseases. Therefore, inhibition of this oxidative damage can be an important part of therapeutic strategies. Pyridoxamine (PM), a prospective drug for treatment of diabetic nephropathy, has been previously shown to inhibit several oxidative and glycoxidative pathways, thus protecting amino acid side chains of the proteins from oxidative damage. Here, we demonstrated that PM can also protect protein backbone from fragmentation induced via different oxidative mechanisms including autoxidation of glucose. This protection was due to hydroxyl radical scavenging by PM and may contribute to PM therapeutic effects shown in clinical trials.
Keywords:Abbreviations: AGE, advanced glycation end-product   BSA, bovine serum albumin   CML, Nε-(carboxymethyl)lysine   PM, pyridoxamine   RNase, bovine pancreatic ribonuclease A
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