Screening study of serum thrombosis-related target proteins using a specific dabigatran-functionalized material

A drug-related protein profiling strategy was developed based on drug-protein interactions, utilizing a magnetic adsorbent modified with dabigatran (Fe₃O₄@SiO₂@DBG). Dabigatran (DBG), the hydrolytic product of dabigatran etexilate, which is a drug for thromboembolic disease treatment, was covalently immobilized on the surface of the Fe₃O₄@SiO₂-NH₂ nanomaterial via amide bonds to screen drug-associated proteins in patient serum based on protein-drug interactions. Healthy human serum was first used as a model sample to evaluate the strategy and optimize the screen procedure. Subsequently, the method was applied to screen drug-related proteins in serum samples from patients with hyperlipidemia/thrombosis/cardiovascular disease (HTC) and healthy controls (HC). A total of 26 differential proteins were identified. Further GO functional annotation and KEGG pathway analyses revealed that these differential proteins and their involved pathways were highly associated with the regulation of metabolic processes and signalling pathways related to HTC diseases, providing guidance for the screening of drug targets or biomarkers of thromboembolic diseases. Collectively, this interaction-oriented protein screening approach provides an innovative technical platform for subsequent mechanism research and related drug development.