title: Assembly of PNA-tagged small molecules, peptides, and carbohydrates onto DNA templates: programming the combinatorial pairing and inter-ligand distance.
abstract: The biochemical stability and desirable hybridization properties of peptide nucleic acids (PNA) coupled to the robustness of the peptidic chemistry involved in their oligomerization make them an attractive nucleic acid tag to encode molecules and program their assembly into higher order oligomers. The ability to program the dimerization of ligands with controlled distance between the ligands has important applications in emulating multimeric interactions. Additionally, the ability to program different permutations of ligand assemblies in a combinatorial fashion provides access to a broad diversity and offers a rapid screening method for fragment based approaches to drug discovery. Herein, we describe protocols to covalently link diverse carbohydrates, peptides, or small molecules to PNA and combinatorially assemble them in solution onto libraries of DNA templates or onto DNA microarrays using a commercial platform without recourse to specialized equipment or heavy upfront investment.
authors.affiliation: Laboratoire de Chemie Organique et Bioorganique, Institut de Science et d'Ingénierie Supramoléculaires, Université Louis Pasteur, Strasbourg, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Winssinger
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gorska
authors.forename: Mihai
authors.initials: M
authors.lastname: Ciobanu
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Daguer
authors.forename: Sofia
authors.initials: S
authors.lastname: Barluenga
mesh_terms: D000595:Amino Acid Sequence; D003062:Codon / Q000235:genetics; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004247:DNA / Q000737:chemistry*; D008024:Ligands; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D020135:Peptide Nucleic Acids / Q000737:chemistry* / Q000235:genetics; D010455:Peptides / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry*
chemical_list: D003062:Codon; D008024:Ligands; D020135:Peptide Nucleic Acids; D010455:Peptides; D011134:Polysaccharides; D054852:Small Molecule Libraries; D004247:DNA