Single-Step Grafting of Aminooxy-Peptides to Hyaluronan: A Simple Approach to Multifunctional Therapeutics for Experimental Autoimmune Encephalomyelitis
J. Sestak1 , Meagan Mullins 1 , Laura Northrup 1 , Shara Thati 1 , Teruna Siahaan 1 , and C. Berkland1, 2
1 Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, 66047; 2 Department of Chemical Engineering, University of Kansas, Lawrence, KS 66407
Two different peptide species, a multiple sclerosis antigen (PLP) and an ICAM-1 ligand (LABL) known to block immune cell stimulation, were simultaneously conjugated to hyaluronic acid in an equimolar ratio using modified oxime chemistry. The resulting hyaluronan with grafted PLP and LABL significantly inhibited disease in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis. Aminooxy-peptides facilitate simple synthesis of multifunctional hyaluronan graft polymers, thus enabling novel approaches to antigenspecific immune modulation.