Preparation and immunological studies of protein conjugates of N -acylneuraminic acids

Glycoconjugate Journal
Peter ChefaloZhongwu Guo

Abstract

The overexpression of N -acetylneuraminic acid (Neu5Ac) is closely correlated with malignant transformations. Thus, Neu5Ac is an important target in the design of cancer vaccines. To study the influence of chemical modifications of Neu5Ac on its immunological properties, the alpha-allyl glycosides of five differently N -acylated neuraminic acid derivatives were prepared. Following selective ozonolysis of their allyl group to form an aldehyde functionality, they were coupled to keyhole limpet hemocyanin (KLH) via reductive amination. Resultant glycoconjugates were studied in C57BL/6 mice. The N -propionyl, N - iso- butanoyl and N -phenylacetyl derivatives of neuraminic acid provoked robust immune responses of various antibody isotypes, including IgM, IgG1, IgG2a and IgG3, whereas N -trifluoropropionylneuraminic acid and natural Neu5Ac were essentially nonimmunogenic. Moreover, the N -phenylacetyl and N - iso- butanoyl derivatives mainly induced IgG responses that are desirable for antitumor applications. These results raise the promise of formulating effective glycoconjugate cancer vaccines via derivatizing sialic acid residues of sialooligosaccharides.

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Citations

Mar 15, 2006·Biochemistry·Peter ChefaloClifford V Harding
Dec 22, 2009·ACS Chemical Biology·Xi Chen, Ajit Varki
Feb 4, 2005·Journal of Medicinal Chemistry·Yanbin PanZhongwu Guo
Aug 14, 2009·Glycobiology·Jian DuKevin J Yarema
Mar 16, 2012·Future Medicinal Chemistry·Rachel Hevey, Chang-Chun Ling
Aug 1, 2010·Expert Opinion on Drug Discovery·Laura CipollaNasrin Shaikh
Jul 29, 2004·Carbohydrate Research·Yanbin PanZhongwu Guo
Jun 30, 2015·The Journal of Organic Chemistry·Mauro PascoluttiMark von Itzstein
Sep 22, 2009·Current Opinion in Chemical Biology·Zhongwu Guo, Qianli Wang
Jul 21, 2016·Angewandte Chemie·Paul R WratilWerner Reutter
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Aug 26, 2009·Journal of Medicinal Chemistry·Pierre StallforthPeter H Seeberger

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