title: Tocilizumab-Alendronate Conjugate for Treatment of Rheumatoid Arthritis.
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 by1H 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.
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH) , 77 Cheongam-ro, Nam-gu, Pohang 790-784, Korea.
authors.forename: Hwiwon
authors.initials: H
authors.lastname: Lee
authors.affiliation: School of Chemical Engineering, Department of Energy Science, Sungkyunkwan University , Suwon 440-746, Korea.
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Bhang
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH) , 77 Cheongam-ro, Nam-gu, Pohang 790-784, Korea.
authors.forename: Jeong Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH) , 77 Cheongam-ro, Nam-gu, Pohang 790-784, Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH) , 77 Cheongam-ro, Nam-gu, Pohang 790-784, Korea.
authors.forename: Sei Kwang
authors.identifier: 0000-0002-7718-6259
authors.initials: SK
authors.lastname: Hahn
mesh_terms: D019386:Alendronate / Q000737:chemistry*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D050071:Bone Density Conservation Agents; D002470:Cell Survival / Q000187:drug effects; D018796:Immunoconjugates / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D008811:Mice, Inbred DBA; D000067996:RAW 264.7 Cells; D055114:X-Ray Microtomography; D000093242:Interleukin-6 Inhibitors
chemical_list: D019386:Alendronate; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D018796:Immunoconjugates; D000093242:Interleukin-6 Inhibitors; C502936:tocilizumab