Synthesis of tumor necrosis factor α for use as a mirror-image phage display target†
Abstract
Tumor Necrosis Factor alpha (TNFα) is an inflammatory cytokine that plays a central role in the pathogenesis of chronic inflammatory disease. Here we describe the chemical synthesis of L-TNFα along with the mirror-image D-protein for use as a phage display target. The synthetic strategy utilized native chemical ligation and desulfurization to unite three peptide segments, followed by oxidative folding to assemble the 52 kDa homotrimeric protein. This synthesis represents the foundational step for discovering an inhibitory D-peptide with the potential to improve current anti-TNFα therapeutic strategies.
- This article is part of the themed collection: Selective Chemistry with Peptides and Proteins