APYTFGQGTK* SIL Adalimumab internal standard – Stable Isotope Labeled (SIL) peptides catalog

Tumor Necrosis Factor α, also known as Cachectin (uniprot P01375),is a cytokine secreted by macrophages to warn other immune cells of an infection. Structurally speaking,TNF- α is a trimer of 233 amino acids whose subunits are essentially organized in a beta-sandwich structure formed by two anti-parallel beta-pleated sheets. TNF-α binds to either TNFR1 and TNFR2 receptors,inducing fever,apoptotic cell death,cachexia,inflammation,and cell death of certain tumor cell lines. It can also inhibit viral replication and respond to sepsis via IL-1 and IL-6 producing cells. Due to its primary role in immune cells regulation,dysregulation of its production has been associated with the pathogenesis of several chronic inflammatory medical conditions including rheumatoid,psoriatic and juvenile idiopathic arthritis,psoriasis and inflammatory bowel disease (IBD),among others. Moreover,its adipokine activity tends to promote insulin resistance leading to obesity-induced type 2 diabetes. Adalimumab is a therapeutic human immunoglobulin G1 (IgG1) anti-TNF-α monoclonal antibody (mAb) prescribed to treat the conditions listed in the table below. It binds specifically and with high affinity to TNF-α,in order to inhibit its interaction with TNFR1 and TNFR2 receptors. Moreover this recombinant Ig has the power to lyse the surface of TNF-expressing cells in vitro in the presence of complements,thus impairing TNF signaling pathway efficiently. Nowadays, hundreds of mAbs are in clinical development,hence the need to establish their pharmacokinetic properties in pre-clinical studies. Even though samples are often analyzed using immunoassays,alternative methods,such as quantitative proteomics by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS),are emerging. In order to quantify proteins of interest by LC-MS/MS,SIL signature peptides are used. In this case,the APYTFGQGTK peptide sequence was chosen for Adalimumab quantification in blood samples. This peptide is part of the mAb's light chain and the increased mass of its heavy peptide counterpart,marked by 13C and 15N-labeled Lysine,allow targeted measurement of Adalimumab level in vitro. For additional Adalimumab MS detection,you can also use IC-PEPTIDE's SIL NYLAWYQQKPGK peptide.

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