An autonomous molecular assembler for programmable chemical synthesis

Abstract

Molecular machines that assemble polymers in a programmed sequence are fundamental to life. They are also an achievable goal of nanotechnology. Here, we report synthetic molecular machinery made from DNA that controls and records the formation of covalent bonds. We show that an autonomous cascade of DNA hybridization reactions can create oligomers, from building blocks linked by olefin or peptide bonds, with a sequence defined by a reconfigurable molecular program. The system can also be programmed to achieve combinatorial assembly. The sequence of assembly reactions and thus the structure of each oligomer synthesized is recorded in a DNA molecule, which enables this information to be recovered by PCR amplification followed by DNA sequencing.

Enzyme-free nucleic acid dynamical systems

“…Furthermore, nucleic acids-both DNA and RNAare well known for their ability to bind to and sense small molecules (68,69), thus providing direct mechanisms to "read" the chemical environment. Nucleic acid nanotechnology has also been applied to control chemical synthesis (70)(71)(72); to control the arrangement (and rearrangement) of metal nanoparticles, quantum dots, carbon nanotubes, proteins, and other molecules (73)(74)(75)(76)(77); and to control the activity of enzymes and protein motors (78)(79)(80). Much as genetic regulatory networks and other biochemical feedback networks control chemical and molecular functions within biological cells, it is conceivable that nucleic acid dynamical systems could serve as the information processing and control networks within complex synthetic or- .…”

DNA‐Based Chemical Reaction Networks

“…Meng et al. programed a DNA‐based assembler system for creating oligomers with defined sequences (Figure ) . This molecular assembler comprises three components: cargo hybridized to strand I to generate the initiator duplex I, chemistry hairpins (i.e., A and B) carrying building blocks, and instruction hairpins (i.e., I>A and A>B) that control assembly.…”

“…Meng et al programedaDNAbased assembler system for creating oligomers with defined sequences (Figure 8). [50] This molecular assembler comprises three components:c argo hybridized to strand It og enerate the initiator duplex I, chemistry hairpins (i.e.,Aand B) carrying buildingb locks, and instruction hairpins (i.e.,I > Aa nd A > B) that control assembly.U sing ar econfigurable molecular program to define as equence, they linked the buildingb locks through olefin or peptideb onds and obtained the synthesized oligomers by hairpin hybridization chain reactions, [7c, 51] in which the yielded product is al inear duplex. In addition, such an autonomous cascade of DNA hybridization reactions allows for combinatorial assembly.N otably,t he sequence of assembly reactions recorded in aD NA molecule can be recoveredb y DNA sequencing.…”

“…To date, materials obtained throughD NA-programmable chemical synthesis have been extended to organicc ompounds, biomacromolecules,p roteins, DNA nanostructures, ands oforth. [48,50,[52][53][54]…”

Active Self‐Assembly of Train‐Shaped DNA Nanostructures via Catalytic Hairpin Assembly Reactions

“…Here, we integrate the catalytic hairpin assembly (CHA) reactions with DNA tiles and explore them as a means to assemble nanostructures dynamically. CHA is a robust enzyme‐free signal‐amplification reaction that has potential applications in biosensing, protein assembly, cargo synthesis . In the present study, we used DNA tiles (little DX tiles and large DNA origami) as artificial “carriages,” hairpin structures modified on DNA tiles as “couplers,” and initiators as “wrenches” to initiate the CHA to actively self‐assemble train‐shaped DNA nanostructures with controlled length.…”