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Chemical Synthesis of GM2 Glycans, Bioconjugation with Bacteriophage Qβ, and the Induction of Anticancer Antibodies
Author(s) -
Yin Zhaojun,
Dulaney Steven,
McKay Craig S.,
Baniel Claire,
Kaczanowska Katarzyna,
Ramadan Sherif,
Finn M. G.,
Huang Xuefei
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500499
Subject(s) - bioconjugation , antibody , chemistry , cytotoxicity , antigen , bacteriophage , biochemistry , biology , microbiology and biotechnology , in vitro , immunology , escherichia coli , gene
The development of carbohydrate‐based antitumor vaccines is an attractive approach towards tumor prevention and treatment. Herein, we focused on the ganglioside GM2 tumor‐associated carbohydrate antigen (TACA), which is overexpressed in a wide range of tumor cells. GM2 was synthesized chemically and conjugated with a virus‐like particle derived from bacteriophage Qβ. Although the copper‐catalyzed azide–alkyne cycloaddition reaction efficiently introduced 237 copies of GM2 per Qβ, this construct failed to induce significant amounts of anti‐GM2 antibodies compared to the Qβ control. In contrast, GM2 immobilized on Qβ through a thiourea linker elicited high titers of IgG antibodies that recognized GM2‐positive tumor cells and effectively induced cell lysis through complement‐mediated cytotoxicity. Thus, bacteriophage Qβ is a suitable platform to boost antibody responses towards GM2, a representative member of an important class of TACA: the ganglioside.