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Tocilizumab-Alendronate Conjugate for Treatment of Rheumatoid Arthritis

Author:
Lee, Hwiwon  Bhang, Suk Ho  Lee, Jeong Ho  Kim, Hyemin  Hahn, Sei Kwang  


Journal:
BIOCONJUGATE CHEMISTRY


Issue Date:
2017


Abstract(summary):

An autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ) Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio)propionyl hydrazide (PDPH) poly(ethylene glycol) N-hydroxysuccinimide (PDPH-PEG-NHS). The successful synthesis of TCZALD conjugate is corroborated by 1H NMR, the purpald assay, mass spectrometry (MS), and high performance liquid chromatography (HPLC). In vitro binding affinity and cell viability tests confirmed the biological activity of TCZ-ALD conjugate. Furthermore, in vivo efficacy of TCZ-ALD conjugate is confirmed by microcomputed tomography (CT), histology, and Western blot analyses for the treatment of RA.


Page:
1084---1092


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