A peptide from the beta-strand region of CD2 protein that inhibits cell adhesion and suppresses arthritis in a mouse model.
Cell adhesion molecules play a central role at every step of the immune response. The function of leukocytes can be regulated by modulating adhesion interactions between cell adhesion molecules to develop therapeutic agents against autoimmune diseases. Among the different cell adhesion molecules that participate in the immunologic response, CD2 and its ligand CD58 (LFA-3) are two of the best-characterized adhesion molecules mediating the immune response. To modulate the cell adhesion interaction, peptides were designed from the discontinuous epitopes of the beta-strand region of CD2 protein. The two strands were linked by a peptide bond. beta-Strands in the peptides were nucleated by inserting a beta-sheet-inducing Pro-Gly sequence with key amino acid sequences from CD2 protein that binds to CD58. Using a fluorescence assay, peptides that exhibited potential inhibitory activity in cell adhesion were evaluated for their ability to bind to CD58 protein. A model for peptide binding to CD58 protein was proposed based on docking studies. Administration of one of the peptides, P3 in collagen-induced arthritis in the mouse model, indicated that peptide P3 was able to suppress rheumatoid arthritis in mice.
Satyanarayanajois
Seetharama D
SD
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA. jois@ulm.edu
Büyüktimkin
Barlas
B
Gokhale
Ameya
A
Ronald
Sharon
S
Siahaan
Teruna J
TJ
Latendresse
John R
JR
D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001665:Binding Sites; D018801:CD2 Antigens / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D018968:CD58 Antigens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D018938:Caco-2 Cells; D002448:Cell Adhesion / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008811:Mice, Inbred DBA; D023421:Models, Animal; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry / Q000627:therapeutic use*; D017433:Protein Structure, Secondary
D018801:CD2 Antigens; D018968:CD58 Antigens; D010456:Peptides, Cyclic