Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2,4-Dinitrophenol / chemistry
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Animals
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Antibody Formation
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Antigens, Tumor-Associated, Carbohydrate / chemistry*
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Antigens, Tumor-Associated, Carbohydrate / immunology
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Cysteine / chemistry
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Cytotoxicity, Immunologic
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Dendrimers / chemical synthesis*
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Dendrimers / chemistry
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Dendrimers / pharmacology
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Epitopes
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Female
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Glycopeptides / chemistry
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Haptens
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Hemagglutinin Glycoproteins, Influenza Virus / chemistry
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Humans
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Immunoglobulin G / biosynthesis
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Immunoglobulin M / biosynthesis
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Jurkat Cells
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Killer Cells, Natural / drug effects*
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Killer Cells, Natural / immunology
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Lectins / chemistry*
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Mice
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Mice, Inbred BALB C
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Plant Lectins / chemistry
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Protein Binding
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Protein Isoforms / chemistry
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Rats
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Receptors, Immunologic / chemistry
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T-Lymphocytes / immunology
Substances
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Antigens, Tumor-Associated, Carbohydrate
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Dendrimers
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Epitopes
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Glycopeptides
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Haptens
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Hemagglutinin Glycoproteins, Influenza Virus
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Immunoglobulin G
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Immunoglobulin M
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Klrb1b protein, rat
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Lectins
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Plant Lectins
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Protein Isoforms
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Receptors, Immunologic
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Tn antigen
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Cysteine
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2,4-Dinitrophenol