Towards a fully synthetic MUC1-based anticancer vaccine: efficient conjugation of glycopeptides with mono-, di-, and tetravalent lipopeptides using click chemistry |
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Authors: | Cai Hui Huang Zhi-Hua Shi Lei Zhao Yu-Fen Kunz Horst Li Yan-Mei |
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Institution: | Department of Chemistry, Tsinghua University, Key Lab of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, PR China. |
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Abstract: | The membrane‐bound tumor‐associated glycoprotein MUC1 is aberrantly glycosylated in cancer cells compared with normal cells, and is therefore considered an attractive target for cancer immunotherapy. However, tumor‐associated glycopeptides from MUC1 do not elicit a sufficiently robust immune response. Therefore, antitumor vaccines were developed, which consist of MUC1 glycopeptides as the B epitopes and immune‐stimulating toll‐like receptor 2 (TLR 2) lipopeptide ligands. These fully synthetic vaccine candidates were prepared by solid‐phase synthesis of the MUC1 glycopeptides. The Pam3Cys lipopeptide, also synthesized on solid‐phase, was C‐terminally coupled to oligovalent lysine cores, which N‐terminally incorporate O‐propargyl oligoethylene glycol acyl side chains. The MUC1 glycopeptides and lipopeptide lysine constructs were then conjugated by click chemistry to give oligovalent synthetic vaccines. Oligovalent glycopeptide–lipopeptide conjugates are considered more immunogenic than their monovalent analogues. |
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Keywords: | antitumor agents click chemistry glycopeptides receptor ligand solid‐phase synthesis |
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