TY - JOUR
T1 - A peptide from the beta-strand region of CD2 protein that inhibits cell adhesion and suppresses arthritis in a mouse model
AU - Satyanarayanajois, Seetharama D.
AU - Büyüktimkin, Barlas
AU - Gokhale, Ameya
AU - Ronald, Sharon
AU - Siahaan, Teruna J.
AU - Latendresse, John R.
PY - 2010/9
Y1 - 2010/9
N2 - 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 β-strand region of CD2 protein. The two strands were linked by a peptide bond. β-Strands in the peptides were nucleated by inserting a β-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.
AB - 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 β-strand region of CD2 protein. The two strands were linked by a peptide bond. β-Strands in the peptides were nucleated by inserting a β-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.
KW - CD2 peptides CD2
KW - CD58
KW - NMR
KW - arthritis mouse model
KW - beta hairpin
KW - cell adhesion
KW - immunomodulation
UR - http://www.scopus.com/inward/record.url?scp=77955257453&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955257453&partnerID=8YFLogxK
U2 - 10.1111/j.1747-0285.2010.01001.x
DO - 10.1111/j.1747-0285.2010.01001.x
M3 - Article
C2 - 20572813
AN - SCOPUS:77955257453
SN - 1747-0277
VL - 76
SP - 234
EP - 244
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
IS - 3
ER -