title: Design of beta-hairpin peptides for modulation of cell adhesion by beta-turn constraint.
abstract: The CD2-CD58 interaction in immune regulation and disease pathology has provided new targets for developing potential immunosuppressive agents. In the present study, we report the introduction of constraints to generate beta-hairpin structures from the strand sequences of CD2 protein. The beta-hairpin structures were induced in the designed peptides by introducing Pro-Gly sequences in the peptides. Results from NMR and MD simulation indicated that the peptides exhibited beta-turn structure at the X-Pro-Gly-Y sequence and formed the beta-hairpin structure in solution. The ability of these peptides to inhibit cell adhesion was evaluated by two cell adhesion assays. Among the peptides studied (1-4) (P1-P4), peptides 2-4 were able to inhibit cell adhesion between Jurkat cells and SRBC nearly 50% at 180 microM, and 80% inhibition between Jurkat cells and Caco-2 cells was seen at 90 microM. Peptide 1 did not show significant inhibition activity compared to control.
authors.affiliation: Department of Basic Pharmaceutical Sciences, University of Louisiana at Monroe, 700 University Avenue, Monroe, Louisiana 71209, USA.
authors.forename: Sumana
authors.initials: S
authors.lastname: Giddu
authors.forename: Vivekanandan
authors.initials: V
authors.lastname: Subramanian
authors.forename: Ho Sup
authors.initials: HS
authors.lastname: Yoon
authors.forename: Seetharama D
authors.initials: SD
authors.lastname: Satyanarayanajois
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018801:CD2 Antigens / Q000737:chemistry*; D018968:CD58 Antigens / Q000737:chemistry; D018938:Caco-2 Cells; D002448:Cell Adhesion / Q000187:drug effects*; D002470:Cell Survival; D015195:Drug Design; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012397:Rosette Formation; D012756:Sheep; D013329:Structure-Activity Relationship
chemical_list: D018801:CD2 Antigens; D018968:CD58 Antigens; D010455:Peptides