Biologics through chemistry: Total synthesis of a proposed dual-acting vaccine targeting ovarian cancer by orchestration of oligosaccharide and polypeptide domains Journal Article
| Authors: | Zhu, J.; Wan, Q.; Ragupathi, G.; George, C. M.; Livingston, P. O.; Danishefsky, S. J. |
| Article 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 Gb3 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<sub>3</sub>-MUC5AC thioester cassette as a key building block. Syntheses of both nonconjugate and KLH-conjugated vaccines constructs have been accomplished. © 2009 American Chemical Society. |
| Keywords: | controlled study; unclassified drug; human cell; t lymphocyte; gene targeting; complex formation; ovary cancer; cell maturation; cell motion; drug design; drug synthesis; cell type; stem cell; simulation; amines; immune response; antigens; cancer vaccine; cancer cell; epitope; cell membranes; tumor immunity; total synthesis; synthesis (chemical); carbohydrates; carbohydrate antigen; chemical synthesis; thioester; cancer cells; vaccines; keyhole limpet hemocyanin; cell membrane permeability; cell degeneration; mucin; cell surface; oligosaccharide; conjugation; anti-tumor; building block; cell surfaces; ovarian cancers; peptide epitopes; t-cell epitopes; polypeptides; cancer antibody; globotriaosylceramide; globotriaosylceramide mucin 5ac conjugate; mucin 5ac; polypeptide; gene cassette |
| Journal Title: | Journal of the American Chemical Society |
| Volume: | 131 |
| Issue: | 11 |
| ISSN: | 0002-7863 |
| Publisher: | American Chemical Society |
| Date Published: | 2009-03-25 |
| Start Page: | 4151 |
| End Page: | 4158 |
| Language: | English |
| DOI: | 10.1021/ja810147j |
| PROVIDER: | scopus |
| PMCID: | PMC2679991 |
| PUBMED: | 19253940 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 14" - "Export Date: 30 November 2010" - "CODEN: JACSA" - "Source: Scopus" |
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23Wan -
144Ragupathi -
14
Zhu -
539Danishefsky -
228Livingston -
10
George
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