DNA micelles as nanoreactors: efficient DNA functionalization with hydrophobic organic molecules

Abstract

We report a micelle-templated method to enhance the reactivity of DNA with highly hydrophobic molecules. Lipids, chromophores and polymers can be conjugated to DNA in high yield and under mild conditions. This method expands the range of DNA-templated reactions for DNA-encoded libraries, oligonucleotide and drug delivery, nanopore mimetics and DNA nanotechnology.

Dual‐Input Regulation and Positional Control in Hybrid Oligonucleotide/Discotic Supramolecular Wires

“…Foldamers consisting of oligonucleotides with extended aromatic molecules integrated into their backbone have resulted in temperature‐responsive structures, and decoration of DNA structures with hydrophobic polymers of diverse length and composition was shown to control the self‐assembly properties of DNA prismatic cages, adding a higher level of complexity . The addition of lipids into DNA scaffolds has led to the development of supramolecular systems with novel functions, as highlighted in recent reviews . DNA hybrid‐grafted supramolecular polymers based on the self‐assembly properties of oligopyrenes have been reported, with the structure of the oligopyrenes dictating the morphology of the final assembly into helical 1D supramolecular polymers and requiring a high temperature to incorporate additional monomers …”

Amphiphilic “Like-A-Brush” Oligonucleotide Conjugates with Three Dodecyl Chains: Self-Assembly Features of Novel Scaffold Compounds for Nucleic Acids Delivery

“…Due to their amphipathic nature, oligonucleotide conjugates with lipophilic groups can self-assemble in aqueous solutions and form micelles [ 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ] and their aggregates [ 10 , 11 , 14 ], vesicular assemblies [ 19 , 20 ], and more complex self-aggregation structures [ 2 , 11 , 21 ]. Generally, these structures are nearly spherical in shape [ 10 , 15 , 16 , 20 , 22 , 23 ]. The size and the shape of self-assembling structures may greatly depend on experimental conditions: ionic strength, pH, and temperature; the type of lipophilic group; the length and nucleotide sequence of an oligomer in the LOC [ 2 , 17 ].…”

High definition polyphosphoesters: between nucleic acids and plastics

“…129 Chemical as well as biological processes can be improved using this system -by hybridising a second oligonucleotide with a reactive amine end to DNA-C1212 micelles, such that its amine is contained within the hydrophobic microenvironment, it was possible to greatly increase the yield of conjugation to NHSactivated carboxylic acids, providing a useful tool for combatting solvent incompatibility in bioconjugation reactions. 130 Elaboration of the monomers available has seen use of a fluorinated side chain unit (Fig. 6b) which can either produce micelles (up to 10 coupled) or placed in the middle of duplexes to increase stability, enable 19 F NMR detection, improve nuclease stability, and increase gene silencing efficacy.…”