Comblike Dendrimers Containing Tn Antigen Modulate Natural Killing and Induce the Production of Tn Specific Antibodies
| Autor: | Karel Bezouška, Rostislav Kuklik, Marian Hajduch, Petr Dzubak, Pavel Veprek, Jana Polakova |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Cytotoxicity
Immunologic Dendrimers Glycoconjugate T-Lymphocytes Tn antigen Hemagglutinin Glycoproteins Influenza Virus Epitope Natural killer cell Epitopes Jurkat Cells Mice Lectins Drug Discovery medicine Animals Humans Protein Isoforms Antigens Tumor-Associated Carbohydrate Cysteine Receptors Immunologic chemistry.chemical_classification Mice Inbred BALB C biology Immunogenicity Glycopeptides Lectin Biological activity Hemagglutinin Rats Killer Cells Natural medicine.anatomical_structure Immunoglobulin M chemistry Biochemistry Immunoglobulin G Antibody Formation biology.protein Molecular Medicine Female Plant Lectins 2 4-Dinitrophenol Haptens Protein Binding |
| Zdroj: | Journal of Medicinal Chemistry. 49:6400-6407 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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