High affinity binding of conformationally constrained synthetic oligomers to an antigen-specific antibody: Discovery of a diagnostically useful synthetic ligand for murine Type 1 diabetes autoantibodies
| Autor: | Scott Simanski, Thomas Kodadek, Patrick J. McEnaney, Todd M. Doran, Yu Gao |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
High affinity binding
Clinical Biochemistry Molecular Conformation Pharmaceutical Science Ligands Biochemistry Oligomer Article Mice Peptoids Structure-Activity Relationship chemistry.chemical_compound Antigen Drug Discovery Animals Molecular Biology Autoantibodies Molecular Structure biology Ligand Organic Chemistry Autoantibody Peptoid Molecular biology Diabetes Mellitus Type 1 chemistry Glycine biology.protein Molecular Medicine Binding Sites Antibody Antibody |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 25:4910-4917 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2015.05.046 |
| Popis: | 'Antigen surrogates' are synthetic, non-natural molecules that recognize the antigen-binding sites of antibodies. These molecules are of interest as replacements for native antigens as antibody 'capture agents' in ELISA-like assays of potential diagnostic utility, for example when the antibody is indicative of a disease state. Antigen surrogates for disease-related antibodies can be mined from one-bead one-compound (OBOC) libraries by first denuding the library of ligands for antibodies present in the serum of control patients or animals, followed by screening the remainder of the library against serum from individuals with a particular disease of interest. Most of the work in this area has been done with peptoids (oligomers of N-alkylated glycine), which provide antibody ligands with only modest affinity and selectivity. Here, we explore the hypothesis that this is due to the 'floppiness' of the peptoid backbone by creating libraries of peptoid-like molecules that have conformation-restricting structural elements inserted into their backbones. Indeed, we show here that these libraries can provide high affinity and selectivity antigen surrogates and that this much-improved binding is completely dependent on conformational restriction of the oligomer chain. |
| Databáze: | OpenAIRE |
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