HDX-MS REVEALS CONFORMATIONAL CHANGES OF IL-23 IN COMPLEX WITH IL-23R/IL-12RB1 AND PHAGE DISPLAY PEPTIDES

摘要

Interleukin IL-23 is a pro-inflammatory cytokine that contributes to the pathogenesis of autoimmune inflammatory diseases. The inhibition of the activity of IL-23 has promising therapeutic effects for psoriasis, psoriatic arthritis, inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis.[1] IL-23 is a heterodimer composed of the cytokine subunits p19 and p40 that bind to the receptor complex IL-23R and IL-12R?1 respectively. The discovery of monoclonal antibodies designed to target IL-23 (either p19 and /or p40) have shown significant efficacy in human studies for some of these diseases. Here we present the application of HDXMS [2] and computational approaches to interrogate the binding interactions of IL-23 with its receptors and the binding epitope of new IL-23 inhibitors such as phage display peptides [3].