Conformationally constrained peptides from CD2 to modulate protein-protein interactions between CD2 and CD58

J Med Chem. 2011 Aug 11;54(15):5307-19. doi: 10.1021/jm200004e. Epub 2011 Jul 14.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD2 Antigens / chemistry*
  • CD2 Antigens / immunology
  • CD58 Antigens / chemistry*
  • CD58 Antigens / immunology
  • Caco-2 Cells
  • Cell Adhesion / drug effects*
  • Cell Adhesion / immunology
  • Cell Survival / drug effects
  • Humans
  • Jurkat Cells
  • Mice
  • Molecular Dynamics Simulation
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / immunology
  • Peptides / pharmacology*
  • Protein Conformation
  • Protein Interaction Mapping
  • Rosette Formation
  • Structure-Activity Relationship
  • T-Lymphocytes / drug effects


  • CD2 Antigens
  • CD58 Antigens
  • Peptides