Structure-activity studies of peptides from the "hot-spot" region of human CD2 protein: development of peptides for immunomodulation.
CD2 is a cell surface protein belonging to the immunoglobulin superfamily (IgSF) that plays a key role in mediating adhesion between human T-lymphocytes and target cells. The interaction between cell-adhesion molecules CD2 and CD58 is critical for immune response. Modulation or inhibition of these interactions has been shown to be therapeutically useful. Synthetic 12-mer linear and cyclic peptides and cyclic hexapeptides from the beta-turn and beta-strand region (hot spot) of human CD2 protein were designed to modulate CD2-CD58 interaction. The 12-amino acid synthetic cyclic peptides effectively blocked the interaction between CD2 and CD58 proteins as demonstrated by E-rosetting and heterotypic adhesion assays. NMR and molecular modeling studies indicated that these cyclic peptides exhibit beta-turn structure in solution and closely mimic the beta-turn structure of the surface epitopes of CD2 protein. The designed cyclic peptides with beta-turn structure have the ability to modulate CD2-CD58 interaction.
Liu
Jining
J
Department of Pharmacy, Medicinal Chemistry Program, Office of Life Sciences, Singapore 117543.
Ying
Jinfa
J
Chow
Vincent T K
VT
Hruby
Victor J
VJ
Satyanarayanajois
Seetharama D
SD
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018801:CD2 Antigens / Q000737:chemistry* / Q000378:metabolism; D018968:CD58 Antigens / Q000378:metabolism; D018938:Caco-2 Cells; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000939:Epitopes; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017433:Protein Structure, Secondary; D012756:Sheep; D012996:Solutions; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D018801:CD2 Antigens; D018968:CD58 Antigens; D000939:Epitopes; D009842:Oligopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D012996:Solutions