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Synthesis of a TLR4 Agonist‐Carbohydrate Antigen Conjugate As A Self‐Adjuvanting Cancer Vaccine
Author(s) -
Lewicky Jordan D.,
Ulanova Marina,
Jiang ZiHua
Publication year - 2016
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201600230
Subject(s) - immunogenicity , antigen , chemistry , disaccharide , epitope , linker , biochemistry , immunostimulant , lipid a , carbohydrate , conjugate vaccine , conjugate , antigenicity , immune system , biology , immunology , lipopolysaccharide , mathematical analysis , mathematics , computer science , operating system
Tumour‐associated carbohydrate antigens (TACAs) are promising targets for therapeutic cancer vaccination efforts. However, an inherent limitation of this approach is the poor immunogenicity of carbohydrate epitopes. In an effort to overcome this problem, a self‐adjuvanting TACA has been targeted and synthesized herein, in which a Toll‐like receptor 4 activating lipid A mimic is employed as an immunostimulant and covalently linked to a broadly expressed TACA, the Thomsen‐Freidenreich (TF) antigen. Individual components were first prepared, including the lipid A mimic, the Galβ(1‐3)GalNAc disaccharide building block, and the tetraethylene glycol‐derived linker. The linker was then coupled with the TF disaccharide, and then with the lipid A mimic, both under HBTU‐mediated peptide coupling condition, to provide the conjugated precursor. Global debenzylation via catalytic hydrogenation afforded the designed self‐adjuvanting TF antigen in overall good yield.