Design, structure and biological activity of beta-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 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 CD2-CD58 proteins as demonstrated by antibody binding, E-rosetting and heterotypic adhesion assays. NMR and molecular modeling studies indicated that the synthetic cyclic peptides exhibit beta-turn structure in solution and closely mimic the beta-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 beta-turn structure have the ability to modulate the CD2-CD58 interaction.
Jining
Liu
L
Department of Pharmacy, National University of Singapore, Singapore.
Makagiansar
Irwan
I
Yusuf-Makagiansar
Helena
H
Chow
Vincent T K
VT
Siahaan
Teruna J
TJ
Jois
Seetharama D S
SD
D000595:Amino Acid Sequence; D000818:Animals; D018801:CD2 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018968:CD58 Antigens / Q000737:chemistry / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D000939:Epitopes; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D051381:Rats; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000378:metabolism*
D018801:CD2 Antigens; D018968:CD58 Antigens; D000939:Epitopes; D010455:Peptides