Virus-like Iron-Gold Heterogeneous Nanoparticles for Drug Target Screening

Abstract

Drug-target recognition has great impacts on revealing mechanisms of pharmacological activities, especially drug resistance and off-target effects. In recent years, chemoproteomics has been widely used for drug target screening and discovery due to its high-throughput, high accuracy, and sensitivity. However, there still remain challenges on how to efficiently and unambiguously track target proteins from complex biological matrices. Herein, we report a drug target screening method based on virus-like iron-gold heterogeneous nanoparticles (Au@Fe3O4 NPs). The unique structure of Au@Fe3O4 NPs not only maintains the magnetism of Fe3O4 NPs to facilitate protein enrichment and purification, but also increases drug modification by introducing more active sites on the surface of Au NPs. After coincubating the drug modified NPs with the cell lysate, the high loading of drug on the surface of Au@Fe3O4 NPs was beneficial for capturing target proteins with low abundance. This well-designed heterogeneous nanomaterial provides a novel strategy for improving the efficiency and accuracy of affinity-based proteomics.

Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools – Chances and Limitations. A Critical Review

“…After convenient time periods, the cells are lyzed, and the cell lysates are incubated with magnetic beads coated with a suitable linker (tetrazin-streptavidin [100] or streptavidin [101]) followed by pulldown and identification of the binding proteins by LC-MS/MS. Another approach uses ferric gold nanoparticles coated with the compound of interest [102]. In a different strategy, compounds of interest are conjugated to fluorophores and in-situ UV-cross-linked to their binding protein partners.…”

Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools—Chances and Limitations: A Critical Review

“…After convenient time periods, the cells are lysed, and the cell lysates are incubated with magnetic beads coated with a suitable linker (tetrazin-streptavidin [105] or streptavidin [106]), followed by pull-down and identification of the binding proteins by LC-MS/MS. Another approach uses ferric gold nanoparticles coated with the compound of interest [107]. In a different strategy, compounds of interest are conjugated to fluorophores and in situ UV-crosslinked to their binding protein partners.…”