Quantitative structure-activity relationship of peptides binding to the class II major histocompatibility complex molecule Aq associated with autoimmune arthritis.
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.
Holm
Lotta
L
Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
Frech
Kristina
K
Dzhambazov
Balik
B
Holmdahl
Rikard
R
Kihlberg
Jan
J
Linusson
Anna
A
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
D024043:Collagen Type II; D000939:Epitopes; D006020:Glycopeptides; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D019151:Peptide Library