Assembly of PNA-Tagged Small Molecules, Peptides, and Carbohydrates onto DNA Templates: Programming the Combinatorial Pairing and Inter-ligand Distance

The biochemical stability and desirable hybridization properties of peptide nucleic acids (PNA) coupled to the robustnessof the peptidic chemistry involved in their oligomerization make them an attractive nucleic acid tag to encode molecules andprogram their assembly into higher order oligomers. The ability to program the dimerization of ligands with controlled distancebetween the ligands has important applications in emulating multimeric interactions. Additionally, the ability to programdifferent permutations of ligand assemblies in a combinatorial fashion provides access to a broad diversity and offers a rapidscreening method for fragment based approaches to drug discovery. Herein, we describe protocols to covalently link diversecarbohydrates, peptides, or small molecules to PNA and combinatorially assemble them in solution onto libraries of
DNA
templatesor onto DNA microarrays using a commercial platform without recourse to specialized equipment or heavy upfront investment.