tailieunhanh - Báo cáo khoa học: Design, structure and biological activity of b-turn peptides of CD2 protein for inhibition of T-cell adhesion

The interaction between cell-adhesion molecules CD2 and CD58 is critical for an immune response. Modulation or inhibition of these interactions has been shown to be thera-peuticallyuseful. Synthetic 12-mer linear and cyclic peptides, and cyclic hexapeptides based on rat CD2 protein, were designed tomodulateCD2–CD58 interaction. The synthetic peptides effectively blocked the interaction between CD2– CD58 proteins as demonstrated by antibody binding, E-rosetting and heterotypic adhesion assays. . | Eur. J. Biochem. 271 2873-2886 2004 FEBS 2004 doi Design structure and biological activity of p-turn peptides of CD2 protein for inhibition of T-cell adhesion Liu Jining1 Irwan Makagiansar3 Helena Yusuf-Makagiansar3 Vincent T. K. Chow2 Teruna J. Siahaan3 and Seetharama D. S. Jois1 1 Department of Pharmacy and department of Microbiology National University of Singapore Singapore 3Department of Pharmaceutical Chemistry The University of Kansas Lawrence KS USA The interaction between cell-adhesion molecules CD2 and CD58 is critical for an 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 based on rat CD2 protein were designed to modulate CD2-CD58 interaction. The synthetic peptides effectively blocked the interaction between CD2CD58 proteins as demonstrated by antibody binding E-rosetting and heterotypic adhesion assays. NMR and molecular modeling studies indicated that the synthetic cyclic peptides exhibit b-turn structure in solution and closely mimic the b-turn structure of the surface epitopes of the CD2 protein. Docking studies of CD2 peptides and CD58 protein revealed the possible binding sites of the cyclic peptides on CD58 protein. The designed cyclic peptides with b-turn structure have the ability to modulate the CD2-CD58 interaction. Keywords CD2 b-turn cyclic peptide E-rosetting LFA-3 CD58 . Accessory molecules CD2-CD58 receptor-ligand pair 1-4 are important for adhesion and costimulation in the normal immune response. The CD2 molecule is a transmembrane glycoprotein expressed on all subsets of T-cells NK cells and lymphokine-activated killer cells all known to be effectors of autoimmune disease and allograft rejection. Its ligand CD58 or leukocyte function associated antigen-3 LFA-3 is also a transmembrane glycoprotein distributed widely on T and B lymphocytes erythrocytes endothelium platelets and