Tocilizumab-Alendronate Conjugate for Treatment of Rheumatoid Arthritis
SCIE
SCOPUS
- Title
- Tocilizumab-Alendronate Conjugate for Treatment of Rheumatoid Arthritis
- Authors
- Lee, H.; Bhang, S.H.; Lee, J.H.; Kim, H.; Hahn, S.K.
- Date Issued
- 2017-04
- Publisher
- AMER CHEMICAL SOC
- Abstract
- 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 TCZ-ALD 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. ? 2017 American Chemical Society.
- Keywords
- alendronic acid; interleukin 6 receptor; tocilizumab; animal cell; animal experiment; animal model; antiinflammatory activity; Article; carbon nuclear magnetic resonance; cell viability; comparative study; controlled study; disease severity; drug binding; drug conjugation; drug efficacy; drug potentiation; drug synthesis; enzyme linked immunosorbent assay; high performance liquid chromatography; immunosuppressive treatment; in vitro study; in vivo study; macrophage; micro-computed tomography; mouse; nonhuman; osteoclast; osteoclast activity; proton nuclear magnetic resonance; rheumatoid arthritis; target cell; Western blotting
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/50688
- DOI
- 10.1021/acs.bioconjchem.7b00008
- ISSN
- 1043-1802
- Article Type
- Article
- Citation
- BIOCONJUGATE CHEMISTRY, vol. 28, no. 4, page. 1084 - 1092, 2017-04
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