MS05-P13 VHHs As Tools In Antibody Assisted Structure Based Drug DiscoveryCytokines such as interleukin-6 (IL6) are attractive therapeutic targets in inflammatory diseases. Interleukin-6 is a secreted cytokine, produced by different cell types, but it originates mainly from macrophages and monocytes at the site of inflammation . IL6 is a multifunctional cytokine and mediates its biological function via a hexameric signaling complex composed of two molecules each of IL6, gp80 and gp130 . It is a key player in immunological response and has been implicated in the pathogenesis of a wide range of inflammatory diseases such as rheumatoid arthritis . Heavy chain only antibodies are produced by the immune system of a limited number of animals, including camels and llamas and due to their small size are an attractive tool for antibody based drug discovery. A number of antigen-binding domain (VHH) antibodies that target IL6 have developed to inhibit the hexameric signaling complex formation. VHH94 was derived from a camel heavy chain antibody isolated after immunization with a interleukin-6-gp80 fusion protein. VHH94 was found to enhance the binding of IL-6 to gp80 potentially through binding to an allosteric site on IL-6 and partially inhibited the signaling of IL6. The combination of X-ray crystallography and NMR spectroscopy are using to provide a clear overall picture of the IL6-VHH94 interaction site.
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Keywords: IL-6, VHH94, Structure