High-throughput carbohydrate microarray analysis of 24 lectins.
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Carbohydrate Sequence↗
Biomedical subjects
Joseph C Manimala
Publications and source records attributed to Joseph C Manimala.
Carbohydrate array analysis of anti-Tn antibodies and lectins reveals unexpected specificities: implications for diagnostic and vaccine development.
The Tn antigen is a carbohydrate antigen expressed in most carcinomas, during embryogenesis, on pathogenic parasites, and on HIV. It has been evaluated extensively as a potential diagnostic marker and several Tn-based vaccines are in clinical trials. Based on discrepancies in the literature regarding Tn expression, we began to question whether antibodies and lectins used routinely to detect the Tn antigen were providing accurate information. To investigate this possibility, a carbohydrate microarray and a highly sensitive assay were developed and three frequently used Tn receptors (HBTn1, Bric111, and VVL-B4) were evaluated. Carbohydrate-array analysis revealed unexpected cross-reactivity with other human carbohydrate epitopes. VVL-B4 bound the Tn antigen, GalNAcalpha1-6Gal, and GalNAcalpha1-3Gal. Bric111 bound the Tn antigen, blood group A, GalNAcalpha1-6Gal, and GalNAcalpha1-3Gal. HBTn1 showed the best selectivity, but still displayed moderate binding to blood group A. Implications for the development of Tn-based diagnostics and vaccines are discussed.
Antibodies↗
Tuning the specificity of a synthetic receptor using a selected nucleic acid receptor.
Because of their relative simplicity, synthetic receptors often lack the selectivity observed for biopolymer receptors, such as aptamers. However, aptamer recognition of ligands is limited by the chemistries inherent in the four canonical nucleotides. Here, we report the design and selection of a ternary complex in which the specificity of a bis-boronic acid synthetic host (1) that binds to various carboxylic acids is tuned by a surrounding aptamer. Although, the synthetic receptor alone has higher selectivity for citrate over DL-tartrate, the formation of the aptamer:receptor complex reversed the organic host selectivity to preferentially bind tartrate. The RNA conformation changed upon the introduction of the synthetic host, consistent with an induced-fit mechanism for binding.
Base Sequence↗