Synthesis of Ganglioside Lactams Corresponding to Gm1-, Gm2-,Gm3-, and GM4-Ganglioside Lactones
(1995) In Journal of the American Chemical Society 117(17). p.4742-4754- Abstract
Ganglioside lactams are potentially useful analogs of ganglioside lactones, which are highly immunogenic derivatives of gangliosides. The lactam corresponding to the GM3-lactone saccharide has been synthesized by sialylation of a suitably protected lactose derivative carrying an azido group in the 2'-position, followed by reduction and ring closure to form GM3-lactam. Glycosylation in the 4-position of the central saccharide unit gave the Gm2- and Gm1-lactam saccharides. By a similar route, a 2-azido-Gal derivative was sialylated and treated as above to give the GM4-lactam saccharide. Deprotection gave the GM2-4-lactam saccharides in water soluble form, whereas attempted... (More)
Ganglioside lactams are potentially useful analogs of ganglioside lactones, which are highly immunogenic derivatives of gangliosides. The lactam corresponding to the GM3-lactone saccharide has been synthesized by sialylation of a suitably protected lactose derivative carrying an azido group in the 2'-position, followed by reduction and ring closure to form GM3-lactam. Glycosylation in the 4-position of the central saccharide unit gave the Gm2- and Gm1-lactam saccharides. By a similar route, a 2-azido-Gal derivative was sialylated and treated as above to give the GM4-lactam saccharide. Deprotection gave the GM2-4-lactam saccharides in water soluble form, whereas attempted deprotection of the Gm1-lactam caused its degradation. The GM3-lactam saccharide was coupled to ceramide, to afford the ganglioside lactam analog, and via a spacer to bovine serum albumin (BSA). The BSA conjugate was used as immunogen to raise monoclonal antibodies that cross-reacted with GM3-lactone. The antibodies were used in a histological staining of murine melanoma cells, clearly showing the presence of GM3-lactone on the cell surface. Keeping the GM2-4-lactam saccharides in D2O at 37 °C for 1 month caused marginal (0—11%) hydrolysis of the lactam ring.
(Less)
- author
- Wilstermann, Michael LU ; Kononov, Leonid O. ; Nilsson, Ulf LU ; Ray, Asim K. and Magnusson, Göran LU
- organization
- publishing date
- 1995-05
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of the American Chemical Society
- volume
- 117
- issue
- 17
- pages
- 13 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- scopus:0029008225
- ISSN
- 0002-7863
- DOI
- 10.1021/ja00122a002
- language
- English
- LU publication?
- yes
- id
- c29f81ae-b2e5-4b15-b58a-d2d22ec3df16
- date added to LUP
- 2023-02-07 09:47:35
- date last changed
- 2023-02-22 13:46:00
@article{c29f81ae-b2e5-4b15-b58a-d2d22ec3df16, abstract = {{<p>Ganglioside lactams are potentially useful analogs of ganglioside lactones, which are highly immunogenic derivatives of gangliosides. The lactam corresponding to the G<sub>M3</sub>-lactone saccharide has been synthesized by sialylation of a suitably protected lactose derivative carrying an azido group in the 2'-position, followed by reduction and ring closure to form G<sub>M3</sub>-lactam. Glycosylation in the 4-position of the central saccharide unit gave the Gm<sub>2</sub>- and Gm1-lactam saccharides. By a similar route, a 2-azido-Gal derivative was sialylated and treated as above to give the G<sub>M4</sub>-lactam saccharide. Deprotection gave the G<sub>M2-4</sub>-lactam saccharides in water soluble form, whereas attempted deprotection of the Gm1-lactam caused its degradation. The G<sub>M3</sub>-lactam saccharide was coupled to ceramide, to afford the ganglioside lactam analog, and via a spacer to bovine serum albumin (BSA). The BSA conjugate was used as immunogen to raise monoclonal antibodies that cross-reacted with G<sub>M3</sub>-lactone. The antibodies were used in a histological staining of murine melanoma cells, clearly showing the presence of G<sub>M3</sub>-lactone on the cell surface. Keeping the G<sub>M2-4</sub>-lactam saccharides in D<sub>2</sub>O at 37 °C for 1 month caused marginal (0—11%) hydrolysis of the lactam ring.</p>}}, author = {{Wilstermann, Michael and Kononov, Leonid O. and Nilsson, Ulf and Ray, Asim K. and Magnusson, Göran}}, issn = {{0002-7863}}, language = {{eng}}, number = {{17}}, pages = {{4742--4754}}, publisher = {{The American Chemical Society (ACS)}}, series = {{Journal of the American Chemical Society}}, title = {{Synthesis of Ganglioside Lactams Corresponding to Gm1-, Gm2-,Gm<sub>3<sup>-</sup></sub>, and G<sub>M4<sup>-</sup></sub>Ganglioside Lactones}}, url = {{http://dx.doi.org/10.1021/ja00122a002}}, doi = {{10.1021/ja00122a002}}, volume = {{117}}, year = {{1995}}, }