title: Towards a fully synthetic MUC1-based anticancer vaccine: efficient conjugation of glycopeptides with mono-, di-, and tetravalent lipopeptides using click chemistry.
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 Pam(3) Cys 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.
authors.affiliation: Department of Chemistry, Tsinghua University, Key Lab of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Zhao
authors.forename: Horst
authors.initials: H
authors.lastname: Kunz
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Li
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D019496:Cancer Vaccines / Q000737:chemistry* / Q000276:immunology*; D002460:Cell Line; D057930:Click Chemistry; D006020:Glycopeptides / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D055666:Lipopeptides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008562:Membrane Glycoproteins / Q000737:chemistry*; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D018396:Mucin-1 / Q000737:chemistry* / Q000276:immunology*; D011485:Protein Binding; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000276:immunology*
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D006020:Glycopeptides; D055666:Lipopeptides; D008562:Membrane Glycoproteins; D018396:Mucin-1; D014614:Vaccines, Synthetic