Synthesis of Cyclic Antigenic MUC1 Mimotopes
Lynch, Andrew R.
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The immune system responds to antigens via specific sequences called epitopes. The antibody binding amino acid epitope PDTRP within the variable tandem repeat (VNTR) domain of the Mucin1 (MUC1) transmembrane epithelial glycoprotein has been found to be a tumor-associated antigen, capable of inducing an immune response. After the epithelial cell undergoes an epithelial mesenchymal transition (EMT), transitioning into a replicating tumor cell, the MUC1 glycoprotein becomes hypoglycosylated thus exposing the underlying VNTR domain to the extracellular environment and becoming immunologically active. We have synthesized a truncated cyclic mimotope (Aza-Pro-Asp-Thr-Pra-Lys) of the VNTR domain via solid-phase peptide synthesis and copper-catalyzed alkyne-azide cycloaddition (CuAAC) and isolated it via HPLC.
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