Understanding Fusion Protein Stability by Forced Degradation and Intact Mass Characterization Using Orthogonal Analytical Techniques
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Etanercept is a recombinant tumor necrosis factor (TNF) receptor- Fc fusion protein widely used for the treatment of autoimmune and inflammatory disorders. Structurally, Etanercept consists of the extracellular ligand-binding domain of the human TNF receptor (p75) fused to the Fc region of human IgG1, forming a homodimeric fusion protein stabilized by disulfide bonds and extensive glycosylation (Figure 1). Due to its complex molecular architecture, including multiple disulfide linkages, N-linked and O-linked glycosylation, and Fc-mediated dimerization, Etanercept is susceptible to both physical and chemical degradation pathways. These may include aggregation, fragmentation, and subtle structural modifications when exposed to elevated temperature conditions.