Synthesis of a structurally defined antigen - Immunostimulant combination for use in cancer vaccines Journal Article
| Authors: | Dullenkopf, W.; Ritter, G.; Fortunato, S. R.; Old, L. J.; Schmidt, R. R. |
| Article Title: | Synthesis of a structurally defined antigen - Immunostimulant combination for use in cancer vaccines |
| Abstract: | Ganglioside GM2 expressed on the cell surface of human cancers is a promising target for immunotherapy because GM2 antibodies are cytotoxic in vitro and GM2 antibody formation can be induced upon vaccination in cancer patients. We recently reported on the efficient chemical synthesis of GM2; clinical trials with these synthetic GM2 conjugated to a purified carrier protein (KLH) are currently under way. In our efforts to generate a totally synthetic GM2 cancer vaccine, we have now synthesized GM2 neoglycolipid 1, which consists of the GM2-tetrasaccharide epitope that is linked through a spacer to the B-cell stimulatory glycolipid 4. Target compound 1 was constructed from the GM2 tetrasaccharide donor 2, the 9-hydroxynonanoate 3 spacer, and the 6-amino-6-deoxy derivative (5) of compound 4. Building block 5 was obtained from Z-protected 6-azido-6-deoxy-N-leucyl-glucosamine derivative 12, which was available from glucosamine by two different approaches; the route with the Z-protected derivative of 4 (10) as intermediate gave the best yields. The neoglycolipid 1 reacted with a number of different GM2-reactive antibodies. Vaccination of rabbits with 1 resulted in induction of antibodies against GM2, thus confirming the viability of this novel concept for the construction of a totally synthetic vaccine. |
| Keywords: | controlled study; unclassified drug; nonhuman; drug targeting; animal experiment; drug synthesis; b lymphocyte; cancer inhibition; antigen; antigens; cancer vaccine; immunostimulation; vaccine production; synthesis; ganglioside gm2; antibody production; keyhole limpet hemocyanin; glycolipids; gangliosides; cancer immunology; ganglioside antibody; rabbit; immunostimulants; article; glucosamine derivative; immunostimulating agent; ganglioside gm2 neoglycolipid; nonanoic acid |
| Journal Title: | Chemistry - A European Journal |
| Volume: | 5 |
| Issue: | 8 |
| ISSN: | 0947-6539 |
| Publisher: | Wiley V C H Verlag Gmbh |
| Date Published: | 1999-08-02 |
| Start Page: | 2432 |
| End Page: | 2438 |
| Language: | English |
| PROVIDER: | scopus |
| DOI: | 10.1002/(SICI)1521-3765(19990802)5:8<2432::AID-CHEM2432>3.0.CO;2-5 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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