Serum Metal Ion-Induced Cross-Linking of Photoelectrochemical Peptides and Circulating Proteins for Evaluating Cardiac Ischemia/Reperfusion.

Patients having experienced the ischemia-reperfusion process are particularly vulnerable to subsequent heart attacks because this process can induce myocardial fibrosis, hallmarked by the release of reactive oxygen species and some proteases, such as cathepsin G, into the circulating blood. If these risk indicators can be monitored from the peripheral serum, early diagnosis and intervention may become a reality. For this purpose, we have designed an assay of free copper ions and cathepsin G in serum using only synthetic small molecules as the biosensing elements. No antibodies are needed to recognize the target protein, and no enzymes are needed to generate and amplify the biosensing signal. In this design, a short peptide can target-specifically recognize protease, while the copper ion in the serum can stimulate the photoelectrochemical activity of the probe, resulting in cross-linking of the serum proteins in a target protein-specific manner. Using this method, serum cathepsin G and free copper ion are found to be significantly elevated in the blood samples collected from patients with acute myocardial infarction and successful percutaneous coronary intervention in comparison with healthy controls, indicating a higher risk of subsequent myocardial injury and cardiovascular events. These results may point to the possible application of the proposed assay to evaluate the severity and prognosis of cardiac ischemia/reperfusion in the near future.