title: Biologics through chemistry: total synthesis of a proposed dual-acting vaccine targeting ovarian cancer by orchestration of oligosaccharide and polypeptide domains.
abstract: Carbohydrate and peptide-based antitumor vaccine constructs featuring clusters of both tumor associated carbohydrate antigens and mucin-like peptide epitopes have been designed, synthesized, and studied. The mucin-based epitopes are included to act, potentially, as T-cell epitopes in order to provoke a strong immune response. Hopefully the vaccine will simulate cell surface architecture, thereby provoking levels of immunity against cancer cell types displaying such characteristics. With this central idea in mind, we designed a new vaccine type against ovarian cancer. Following advances in glycohistology, our design is based on clusters of Gb(3) antigen and also incorporates a MUC5AC peptide epitope. The vaccine is among the most complex targeted constructs to be assembled by chemical synthesis to date. The strategy for the synthesis employed a Gb(3)-MUC5AC thioester cassette as a key building block. Syntheses of both nonconjugate and KLH-conjugated vaccines constructs have been accomplished.
authors.affiliation: Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 YorkAVenue, New York, New York 10065, USA.
authors.forename: Jianglong
authors.initials: J
authors.lastname: Zhu
authors.forename: Qian
authors.initials: Q
authors.lastname: Wan
authors.forename: Govind
authors.initials: G
authors.lastname: Ragupathi
authors.forename: Constantine M
authors.initials: CM
authors.lastname: George
authors.forename: Philip O
authors.initials: PO
authors.lastname: Livingston
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Danishefsky
mesh_terms: D000951:Antigens, Neoplasm / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000138:chemical synthesis*; D015195:Drug Design; D005260:Female; D006801:Humans; D055271:Mucin 5AC / Q000627:therapeutic use; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000628:therapy*; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009844:Oligosaccharides; D010455:Peptides