Ammous-Boukhris Nihel, Mosbah Amor, Sahli Emna, Ayadi Wajdi, Hadhri-Guiga Boutheina, Chérif Ameur, Gargouri Ali, Mokdad-Gargouri Raja
LBME, Center of Biotechnology of Sfax, University of Sfax, 3018 Sfax, Tunisie.
BVBGR-LR 11ES31, ISBST University of Manouba, Biotechpole Sidi Thabet, 2020 Ariana, Tunisie.
Peptides. 2016 Nov;85:73-79. doi: 10.1016/j.peptides.2016.09.008. Epub 2016 Sep 17.
Latent membrane protein 1 (LMP1), a major oncoprotein of Epstein Barr Virus (EBV) is responsible for transforming B lymphocytes in vitro. LMP1 is overexpressed in several EBV-associated malignancies, and different approaches have been developed to reduce its level and accordingly its oncogenic function in tumor tissues. This study aimed to use phage display peptide library to obtain peptides which could specifically bind to the cytoplasmic region of LMP1 to prevent its interaction with signaling proteins. The LMP1 C-terminus region was produced in bacterial E. coli and used as target for the phage library panning. After 3 rounds, 20 phage clones were randomly selected and 8 showed high binding affinity to the recombinant C-terminus LMP1 protein. The most interesting candidates are the FO5 "QPTKDSSPPLRV" and NO4 "STTSPPAVPHNN" peptides since both bind the C-terminus LMP1 as showed by molecular docking. Furthermore, sequence alignment revealed that the FO5 peptide shared sequence similarity with the Death Receptor 4 which belongs to the tumor necrosis factor-related apoptosis-inducing receptor which plays key role in anti-tumor immunity.
潜伏膜蛋白1（LMP1）是EB病毒（EBV）的一种主要癌蛋白，负责在体外转化B淋巴细胞。LMP1在几种EBV相关恶性肿瘤中过度表达，并且已经开发出不同的方法来降低其水平，从而降低其在肿瘤组织中的致癌功能。本研究旨在利用噬菌体展示肽库获得能够特异性结合LMP1胞质区域以阻止其与信号蛋白相互作用的肽。LMP1 C末端区域在大肠杆菌中产生，并用作噬菌体库淘选的靶标。三轮后，随机选择20个噬菌体克隆，其中8个对重组C末端LMP1蛋白表现出高结合亲和力。最有趣的候选肽是FO5“QPTKDSSPPLRV”和NO4“STTSPPAVPHNN”肽，因为分子对接显示两者都与C末端LMP1结合。此外，序列比对显示FO5肽与死亡受体4具有序列相似性，死亡受体4属于肿瘤坏死因子相关凋亡诱导受体，在抗肿瘤免疫中起关键作用。
