title: Phage-display screening identifies LMP1-binding peptides targeting the C-terminus region of the EBV oncoprotein.
abstract: 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.
authors.affiliation: LBME, Center of Biotechnology of Sfax, University of Sfax, 3018 Sfax, Tunisie.
authors.forename: Nihel
authors.initials: N
authors.lastname: Ammous-Boukhris
authors.affiliation: BVBGR-LR 11ES31, ISBST University of Manouba, Biotechpole Sidi Thabet, 2020 Ariana, Tunisie.
authors.forename: Amor
authors.initials: A
authors.lastname: Mosbah
authors.affiliation: LBME, Center of Biotechnology of Sfax, University of Sfax, 3018 Sfax, Tunisie.
authors.forename: Emna
authors.initials: E
authors.lastname: Sahli
authors.affiliation: LBME, Center of Biotechnology of Sfax, University of Sfax, 3018 Sfax, Tunisie.
authors.forename: Wajdi
authors.initials: W
authors.lastname: Ayadi
authors.affiliation: LBME, Center of Biotechnology of Sfax, University of Sfax, 3018 Sfax, Tunisie.
authors.forename: Boutheina
authors.initials: B
authors.lastname: Hadhri-Guiga
authors.affiliation: BVBGR-LR 11ES31, ISBST University of Manouba, Biotechpole Sidi Thabet, 2020 Ariana, Tunisie.
authors.forename: Ameur
authors.initials: A
authors.lastname: Chérif
authors.affiliation: LBME, Center of Biotechnology of Sfax, University of Sfax, 3018 Sfax, Tunisie.
authors.forename: Ali
authors.initials: A
authors.lastname: Gargouri
authors.affiliation: LBME, Center of Biotechnology of Sfax, University of Sfax, 3018 Sfax, Tunisie. Electronic address: raja.gargouri@cbs.rnrt.tn.
authors.forename: Raja
authors.initials: R
authors.lastname: Mokdad-Gargouri
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019151:Peptide Library; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015513:Oncogene Proteins; D019151:Peptide Library; D010455:Peptides; D014763:Viral Matrix Proteins
keywords: LMP1; Molecular docking; Oncoprotein; Peptide; Phage display