Modified IL-2 variants that selectively activate regulatory T cells for the treatment of autoimmune diseases
A technology of IL-2 and variants, applied in allergic diseases, chemical instruments and methods, carrier binding/immobilizing peptides, etc., can solve problems such as protein aggregation, inappropriateness, and protein misfolding
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[0088] The following examples are offered by way of illustration only and not by way of limitation. Those skilled in the art will readily recognize that various noncritical parameters can be changed or modified to produce substantially similar results.
[0089] 1. Prediction of candidate PEG attachment sites in IL-2
[0090] To select candidate sites for conjugation of PEG to IL-2, amino acid residues that were exposed to solvent and did not appear to directly or sterically interfere with IL-2 binding to IL-2Rαβγ were identified. strategy in figure 2 displayed in the diagram. Examination of the published crystal structure of IL-2 in complex with the extracellular domain of the IL-2Rαβγ receptor (Wang, X., et al., 2005, Science 310:1159-63, Stauber, D.J., et al., 2006, Proc. Natl Acad Sci 103:2788-93) identified the following residues: S6, K8, K48, K49, T51, E52, K54, K97, G98, F103, M104, E106, D109 and T133 ( image 3 ). Additional amino acid residues that were not visi...
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