title: Conformationally constrained peptides from CD2 to modulate protein-protein interactions between CD2 and CD58.
abstract: Cell adhesion molecule CD2 and its ligand CD58 provide good examples of protein-protein interactions in cells that participate in the immune response. To modulate the cell adhesion interaction, peptides were designed from the discontinuous epitopes of the β-strand region of CD2 protein. The two strands were linked by a peptide bond. β-Strands in the peptides were nucleated by inserting a β-sheet-inducing (D)-Pro-Pro sequence or a dibenzofuran (DBF) turn mimetic with key amino acid sequences from CD2 protein that binds to CD58. The solution structures of the peptides (5-10) were studied by NMR and molecular dynamics simulations. The ability of these peptides to inhibit cell adhesion interaction was studied by E-rosetting and lymphocyte epithelial assays. Peptides 6 and 7 inhibit the cell adhesion activity with an IC(50) of 7 and 11 nM, respectively, in lymphocyte epithelial adhesion assay. NMR and molecular modeling results indicated that peptides 6 and 7 exhibited β-hairpin structure in solution.
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana 71201, United States.
authors.forename: Ameya
authors.initials: A
authors.lastname: Gokhale
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Weldeghiorghis
authors.forename: Veena
authors.initials: V
authors.lastname: Taneja
authors.forename: Seetharama D
authors.initials: SD
authors.lastname: Satyanarayanajois
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018801:CD2 Antigens / Q000737:chemistry* / Q000276:immunology; D018968:CD58 Antigens / Q000737:chemistry* / Q000276:immunology; D018938:Caco-2 Cells; D002448:Cell Adhesion / Q000187:drug effects* / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology*; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D012397:Rosette Formation; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D018801:CD2 Antigens; D018968:CD58 Antigens; D010455:Peptides