Inhibition of cell adhesion and immune responses in the mouse model of collagen‐induced arthritis with a peptidomimetic that blocks CD2‐CD58 interface interactions. Issue 6 (November 2015)

• Record Type: Journal Article
• Authors: Gokhale, Ameya S.; Sable, Rushikesh; Walker, Jason D.; McLaughlin, Leslie; Kousoulas, Konstantin G.; Jois, Seetharama D.
• Is Part Of: Biopolymers. Volume 104:Issue 6(2015)
• Page Start: 733
• Page End: 742
• Publication Date: 2015-11
• Subjects: peptidomimetic -- immunomodulation -- rheumatoid arthritis -- costimulatory molecules -- protein−protein interaction; Biopolymers -- Periodicals; Peptides -- Periodicals; Spectrum analysis -- Periodicals; 572.33
• DOI: 10.1002/bip.22692
• Languages: English
• ISSNs: 0006-3525

Abstract

ABSTRACT: CD2 and CD58 are two important costimulatory molecules involved in generating the signal II required for normal immune signaling. However, this interaction can be targeted to be of benefit in cases of abnormal immune signaling seen in autoimmune diseases. Our objective in this study was to design a peptidomimetic (compound 7) based on a β‐strand structure of the adhesion domain of CD2 protein to inhibit CD2‐CD58 protein‐protein interaction and its effect on immunomodulation in the collagen‐induced arthritis (CIA) model. The ability of compound 7 to bind to CD58 protein was assessed using flow cytometry. The effect of compound 7 on modulating the immune response was evaluated in an autoimmune disease using CIA in mice. The stability of compound 7 was evaluated in mouse serum using mass spectrometry. Antibody (Ab) binding inhibition studies suggested that compound 7 binds to CD58 protein. Compound7 was successful in modulating immune responses when administered in the CIA mouse model along with reducing anti‐collagen Ab levels and decreasing the level of interferon gamma (IFN‐γ) relative to control treatments. Compound7 was found to be nonimmunogenic and stable in mouse serum up to 48 h. Results suggest that compound7 can serve as a lead compound for immunomodulation, and could be a therapeutic agent for the autoimmune disease rheumatoid arthritis (RA). © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 733–742, 2015.