Synthesis of N,N'-bis(acrylamido)acetic acid-based T-antigen glycodendrimers and their mouse monoclonal IgG antibody binding properties.
कीवर्ड
सार
Novel glycodendrimers based on N,N'-bis(acrylamido)acetic acid core with valencies between two and six were synthesized. The breast cancer-associated T-antigen carbohydrate marker, (beta-Gal-(1-3)-alpha-GalNAc-OR), was then conjugated by (i) 1,4-conjugate addition of thiolated T-antigen to the N-acrylamido dendritic cores and by (ii) amide bond formation between an acid derivative of the T-antigen and the polyamino dendrimers. The protein-binding ability of these new glycodendrimers was fully demonstrated by turbidimetric analysis and by enzyme-linked immunosorbent assay (ELISA) using peanut lectin from Arachis hypogaea and a mouse monoclonal antibody (MAb) FAA-J11 (IgG3). When tested as inhibitors of binding between MAb and a polymeric form of the T-antigen (T-antigen-co-polyacrylamide) used as a coating antigen, di- (17), tetra- (20), hexa- (21), and tetravalent (22) dendrimers showed IC(50) values of 174, 19, 48, and 18 nM, respectively. Two tetramers showed 120- to approximately 128-fold increased inhibitory properties over the monovalent antigen 6 used as a standard (IC(50) 2.3 mM). Heterobifunctional glycodendrimer bearing a biotin probe was also prepared for cancer cell labeling.