A peptide from the beta-strand region of CD2 protein that inhibits cell adhesion and suppresses arthritis in a mouse model

Seetharama D. Satyanarayanajois, Barlas Büyüktimkin, Ameya Gokhale, Sharon Ronald, Teruna J. Siahaan, John R. Latendresse

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)234-244
Number of pages11
JournalChemical Biology and Drug Design
Volume76
Issue number3
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

Fingerprint

Cell adhesion
Cell Adhesion
Arthritis
Cell Adhesion Molecules
Peptides
Proteins
prolylglycine
Adhesion
CD58 Antigens
Experimental Arthritis
Cell Communication
Autoimmune Diseases
Epitopes
Amino Acid Sequence
Assays
Rheumatoid Arthritis
Leukocytes
Collagen
Fluorescence
beta-Strand Protein Conformation

Keywords

  • arthritis mouse model
  • beta hairpin
  • CD2 peptides CD2
  • CD58
  • cell adhesion
  • immunomodulation
  • NMR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

A peptide from the beta-strand region of CD2 protein that inhibits cell adhesion and suppresses arthritis in a mouse model. / Satyanarayanajois, Seetharama D.; Büyüktimkin, Barlas; Gokhale, Ameya; Ronald, Sharon; Siahaan, Teruna J.; Latendresse, John R.

In: Chemical Biology and Drug Design, Vol. 76, No. 3, 01.09.2010, p. 234-244.

Research output: Contribution to journalArticle

Satyanarayanajois, Seetharama D. ; Büyüktimkin, Barlas ; Gokhale, Ameya ; Ronald, Sharon ; Siahaan, Teruna J. ; Latendresse, John R. / A peptide from the beta-strand region of CD2 protein that inhibits cell adhesion and suppresses arthritis in a mouse model. In: Chemical Biology and Drug Design. 2010 ; Vol. 76, No. 3. pp. 234-244.
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