Quantitative Chemoproteomic Profiling of Targets of Au(I) Complexes by Competitive Activity-Based Protein Profiling

Abstract

Owing to the encouraging pharmacological action and acceptable toxicity profile, Au(I) complexes have attracted growing interest in the application of disease treatment. In order to investigate their potential target proteins and related bioinformation, herein, we screened four Au(I) complexes and explored the binding proteins utilizing a competitive activity-based protein profiling (ABPP) strategy, including identification experiments and reactivity classification experiments, which offers a simple and robust method to identify the target proteins of Au(I) complexes. We quantified the target proteins of the four Au(I) complexes and found that most of proteins were associated with cancer. In addition, the newly Au(I)-binding proteins and biological gold− protein interaction pathways were exhibited. Furthermore, we estimated the correlation between target proteins of Au(I) complexes and various cancers, which will promote the development of the gold anticancer drugs.

Quantitative Chemoproteomic Methods for Reactive Cysteinome Profiling

“…Global chemoproteomic profiling revealed that itaconate covalently modified key cysteines in fructosebisphosphate aldolase A (ALDOA) and inhibited its enzyme activity, resulting in impairment of glycolytic flux and attenuation of the inflammatory response in stimulated macrophages. Moreover, considering cysteine often serves as a metal-chelating residue, this competitive method has also been exploited to identify metal-binding sites in proteomes, including zinc, [96] gold [97] and iron-sulfur cluster (FeÀ S). [98] In addition to endogenous metabolites, ABPP is a powerful strategy for target identification of natural products.…”

Profiling protein targets of cellular toxicant exposure

“…92 The activity based-protein profiling approach is not limited to electrophiles. Several groups have developed probes to discover protein targets of metal complexes harboring gold, [93][94][95] arsenic, [96][97][98] and platinum. 99 An interesting discovery found using this approach in A549 cells is that strongly arsenicbinding proteins are dominated by anti-oxidant proteins such as thioredoxin and peroxiredoxin.…”