Petersen Mark E, Jacobsen Michael T, Kay Michael S
Department of Biochemistry, University of Utah, 15 N Medical Drive East, Rm 4100, Salt Lake City, Utah 84112-5650, USA.
Org Biomol Chem. 2016 Jun 21;14(23):5298-303. doi: 10.1039/c6ob00824k. Epub 2016 May 23.
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.
肿瘤坏死因子α（TNFα）是一种炎症细胞因子，在慢性炎症性疾病的发病机制中起核心作用。在此，我们描述了l-TNFα及其镜像d蛋白的化学合成，用作噬菌体展示靶点。合成策略利用天然化学连接和脱硫来连接三个肽段，随后进行氧化折叠以组装52 kDa的同三聚体蛋白。这种合成代表了发现一种具有改善当前抗TNFα治疗策略潜力的抑制性d肽的基础步骤。
