design of glycopeptides used to investigate class ii mhc binding and t-cell responses associated with autoimmune arthritis糖肤设计用于调查二类mhc绑定和t细胞反应与自身免疫性关节炎有关.pdfVIP

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design of glycopeptides used to investigate class ii mhc binding and t-cell responses associated with autoimmune arthritis糖肤设计用于调查二类mhc绑定和t细胞反应与自身免疫性关节炎有关.pdf

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design of glycopeptides used to investigate class ii mhc binding and t-cell responses associated with autoimmune arthritis糖肤设计用于调查二类mhc绑定和t细胞反应与自身免疫性关节炎有关

Design of Glycopeptides Used to Investigate Class II MHC Binding and T-Cell Responses Associated with Autoimmune Arthritis 1. 1. 2 2 Ida E. Andersson , C. David Andersson , Tsvetelina Batsalova , Balik Dzhambazov , Rikard 2 1,3 3 Holmdahl , Jan Kihlberg , Anna Linusson * ˚ ˚ 1 Department of Chemistry, Umea University, Umea, Sweden, 2 Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, ¨ ¨ Stockholm, Sweden, 3 AstraZeneca RD Molndal, Molndal, Sweden Abstract The glycopeptide fragment CII259–273 from type II collagen (CII) binds to the murine Aq and human DR4 class II Major Histocompatibility Complex (MHC II) proteins, which are associated with development of murine collagen-induced arthritis (CIA) and rheumatoid arthritis (RA), respectively. It has been shown that CII259–273 can be used in therapeutic vaccination of CIA. This glycopeptide also elicits responses from T-cells obtained from RA patients, which indicates that it has an important role in RA as well. We now present a methodology for studies of (glyco)peptide-receptor interactions based on a combination of structure-based virtual screening, ligand-based statistical molecular design and biological evaluations. This methodology included the design of a CII259–273 glycopeptide library in which two anchor positions crucial for binding in pockets of Aq and DR4 were varied. Synthesis and biological evaluation of the designed glycopeptides provided novel structure-activity relations