Preparation and immunological studies of protein conjugates of N -acylneuraminic acids.
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.
Chefalo
Peter
P
Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Pan
Yanbin
Y
Nagy
Nancy
N
Harding
Clifford
C
Guo
Zhongwu
Z
D000818:Animals; D019496:Cancer Vaccines / Q000737:chemistry; D002240:Carbohydrate Sequence; D002471:Cell Transformation, Neoplastic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006001:Glycoconjugates / Q000737:chemistry; D006433:Hemocyanins / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D008956:Models, Chemical; D009438:Neuraminic Acids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000276:immunology; D009844:Oligosaccharides / Q000737:chemistry; D010126:Ozone; D012794:Sialic Acids / Q000737:chemistry
D019496:Cancer Vaccines; D006001:Glycoconjugates; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009438:Neuraminic Acids; D009844:Oligosaccharides; D012794:Sialic Acids; D010126:Ozone; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin