title: Synthetic MUC1 Antitumor Vaccine Candidates with Varied Glycosylation Pattern Bearing R/S-configured Pam3 CysSerLys4.
abstract: The Toll-like receptor 2 ligand Pam3 CysSer is of particular interest for the construction synthetic vaccines because of its ability to stimulate of the innate immune system. Such vaccines usually comprise Pam3 CysSer with the natural R-configuration at the glycerol 2-position. Pam3 CysSer peptide vaccines with natural configuration have been shown to be more efficient than the corresponding R/S diastereomers. In order to clarify whether the effect of the configuration of Pam3 Cys on the immune response also applies to glycopeptide vaccines, MUC1 glycopeptide-lipopeptide vaccines bearing either R- or R/S-configured Pam3 CysSerLys4 were compared for their immunological effects. In order to find out whether glycosylated MUC1 tandem repeat domains comprise not only B-cell epitopes but also T-cell epitopes, two-component vaccines containing the Pam3 CysSerLys4 lipopeptide and MUC1 glycopeptides with various glycosylation patterns were synthesized, and their immune reactions in mice were studied.
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and, Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and, Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and, Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Huang
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and, Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.
authors.forename: Zhan-Yi
authors.initials: ZY
authors.lastname: Sun
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and, Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Chen
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and, Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Zhao
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg University of Mainz, Duesbergweg 10-14, 55128, Mainz, Germany. hokunz@uni-mainz.de.
authors.forename: Horst
authors.initials: H
authors.lastname: Kunz
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and, Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China. liym@mail.tsinghua.edu.cn.
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Li
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006020:Glycopeptides / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D007109:Immunity / Q000187:drug effects; D008074:Lipoproteins / Q000276:immunology* / Q000627:therapeutic use; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D018396:Mucin-1 / Q000276:immunology* / Q000627:therapeutic use; D060327:Solid-Phase Synthesis Techniques; D013237:Stereoisomerism; D014614:Vaccines, Synthetic / Q000737:chemistry
chemical_list: D019496:Cancer Vaccines; D006020:Glycopeptides; D008074:Lipoproteins; D018396:Mucin-1; D014614:Vaccines, Synthetic; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine
keywords: MUC1 glycopeptides; antibodies; antitumor agents; toll-like receptor 2 ligand; tumor-associated carbohydrate antigens