title: Quantitative structure-activity relationship of peptides binding to the class II major histocompatibility complex molecule Aq associated with autoimmune arthritis.
abstract: Presentation of (glyco)peptides by the class II major histocompatibility complex molecule Aq to T cells plays a central role in collagen-induced arthritis, an animal model for the autoimmune disease rheumatoid arthritis. A peptide library was designed using statistical molecular design in amino acid space in which five positions in the minimal mouse collagen type II binding epitope CII260-267 were varied. A substantially reduced peptide library of 24 peptides with diverse and representative molecular characteristics was selected, synthesized, and evaluated for the binding strength to Aq. A multivariate QSAR model was established by correlating calculated descriptors, compressed to its principle properties, with the binding data using partial least-square regression. The model was successfully validated by an external test set. Interpretation of the model provided a molecular property binding motif for peptides interacting with Aq. The information may be useful in future research directed toward new treatments of rheumatoid arthritis.
authors.affiliation: Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Lotta
authors.initials: L
authors.lastname: Holm
authors.forename: Kristina
authors.initials: K
authors.lastname: Frech
authors.forename: Balik
authors.initials: B
authors.lastname: Dzhambazov
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Jan
authors.initials: J
authors.lastname: Kihlberg
authors.forename: Anna
authors.initials: A
authors.lastname: Linusson
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001665:Binding Sites; D002460:Cell Line; D018920:Coculture Techniques; D024043:Collagen Type II / Q000737:chemistry; D015195:Drug Design; D000939:Epitopes; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006825:Hybridomas; D007376:Interleukin-2 / Q000378:metabolism; D016018:Least-Squares Analysis; D051379:Mice; D008958:Models, Molecular; D019151:Peptide Library; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D024043:Collagen Type II; D000939:Epitopes; D006020:Glycopeptides; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D019151:Peptide Library