Nucleic Acid-programmed Assemblies: Translating Instruction into Function in Chemical Biology

Abstract

The predictability of nucleic acid hybridization offers an attractive platform to program the assembly of tagged ligands or reactants. Hybridization can be used to display multiple ligands in order to gain affinity and/ or selectivity through the cooperative interaction of each ligand. Additionally, hybridization of tagged reagents increases their effective concentration and accelerates reactions. In both cases, an oligonucleotide directs an assembly to yield a functional output in the form of enhanced binding, inhibition, or reaction; for example, a reaction can be used to unmask a fluorophore or a bioactive molecule. This review provides an account of our research in this area as well as future directions.

Multivalent L Kγ-PNA oligomers bind to a human telomere DNA G-rich sequence to form quadruplexes

“…38–41 Previous work has demonstrated the advantageous properties of using a PNA to target proteins via multvalent display. 38, 39, 42–47 …”

Targeted Delivery of Cytotoxic Drugs: Challenges, Opportunities and New Developments

“…Nowadays, fully human monoclonal antibodies can be rapidly isolated from large combinatorial phage display libraries, containing billions of different specificities. [24] The advent of DNA-encoded combinatorial chemical libraries allows the creation and screening of compound collections of unprecedented size,[25–30] thus facilitating ligand discovery. These libraries are composed of small organic molecules, individually attached to distinctive DNA fragments serving as amplifiable identification barcodes.…”

Screening of Three Transition Metal‐Mediated Reactions Compatible with DNA‐Encoded Chemical Libraries

“…[1 -11] Libraries containing billions of compounds from a relatively small number of building blocks (e. g., few thousand chemical compounds) can be constructed using a variety of different experimental approaches, such as pool-and-split methodologies, [12] DNA-templated chemical reactions with preformed oligonucleotide derivatives, [13 -15] or the use of encoded self-assembling strategies. [16][17][18][19][20][21] The attractiveness of encoding chemical compounds with DNA fragments relate to the possibility of constructing and storing large libraries as a mixture, that can be interrogated by affinity capture procedures on immobilized proteins of interest, followed by decoding, using high-throughput DNA sequencing. [12,22,23] Indeed, the identity and relative frequency of each compound in the library (e. g., before and after a screening experiment) can be directly retrieved from the results of a DNA sequencing experiment, since each library member is encoded by a distinctive DNA fragment.…”