Comblike dendrimers containing Tn antigen modulate natural killing and induce the production of Tn specific antibodies.
Comblike glycodendrimers were prepared by the chemoselective ligation of cysteine-modified glycopeptides (1-7) with a 3-maleimidopropionate-modified linear synthetic carrier (8). Glycodendrimers bearing mono-, di-, or tri-Tn clusters (9-11) were tested as inhibitors using plant and mammalian lectins. In the former group, the Codium fragile lectin showed moderate discrimination among 9, 10, and 11. In the latter group, A and B isoforms of rat NKR-P1 lectin strongly discriminated between 9 and 10. 10 caused a 4-fold increase in killing of the NK resistant tumor cell lines at concentrations as low as 10(-8) M. Surprisingly, 11 interacted exclusively with the rat NKR-P1B isoform and inhibited efficiently natural killing in both rats and humans, even in the presence of the activating compounds 9 and 10. Dinitrophenol haptenization or influenza virus hemagglutinin T-cell epitope conjugation increased the immunogenicity of the parent compounds and resulted in the production of Tn specific antibodies.
Veprek
Pavel
P
Group of Glycoconjugates, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 16610 Prague 6, Czech Republic. veprek@uochb.cas.cz
Hajdúch
Marian
M
Dzubak
Petr
P
Kuklík
Rostislav
R
Polakova
Jana
J
Bezouska
Karel
K
D019297:2,4-Dinitrophenol / Q000737:chemistry; D000818:Animals; D000917:Antibody Formation; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry* / Q000276:immunology; D003545:Cysteine / Q000737:chemistry; D003602:Cytotoxicity, Immunologic; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000939:Epitopes; D005260:Female; D006020:Glycopeptides / Q000737:chemistry; D006241:Haptens; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D037102:Lectins / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D037121:Plant Lectins / Q000737:chemistry; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry; D051381:Rats; D011971:Receptors, Immunologic / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology
D015295:Antigens, Tumor-Associated, Carbohydrate; D050091:Dendrimers; D000939:Epitopes; D006020:Glycopeptides; D006241:Haptens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C479632:Klrb1b protein, rat; D037102:Lectins; D037121:Plant Lectins; D020033:Protein Isoforms; D011971:Receptors, Immunologic; C040286:Tn antigen; D003545:Cysteine; D019297:2,4-Dinitrophenol