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Biological Chemistry

Chemists Build Synthetic Polymers From A DNA Blueprint

Technique precisely controls polymer sequence and structure, and it doesn’t require enzymes

by Carmen Drahl
March 4, 2013 | A version of this story appeared in Volume 91, Issue 9

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This macrocyclic building block includes a polymer fragment with coupling groups at each end, a cleavable disulfide linker, and an adapter that mediates the interaction with a DNA template.
An illustration showing each of Liu's macrocyclic building blocks with a polymer fragment that has coupling groups at each end, as well as a cleavable disulfide linker and an adapter for interacting with a DNA template.
This macrocyclic building block includes a polymer fragment with coupling groups at each end, a cleavable disulfide linker, and an adapter that mediates the interaction with a DNA template.

Synthetic polymers make great sensors or self-healing materials, but biological polymers such as proteins have an advantage—the ability to evolve. Chemists would like to evolve synthetic polymers with new applications in the same way nature evolves proteins. However, the strategies developed so far have led to polymers that look like DNA or RNA, because the polymer building blocks must somehow interact with a nucleic acid template. Harvard University’s Jia Niu, Ryan Hili, and David R. Liu have found they can overcome that limitation by using an adapter to interact with the template instead (Nat. Chem., DOI: 10.1038/nchem.1577). Their adapters correspond to DNA sequences that define polymer fragments. They are conceptually similar to the tRNA adapters nature uses to make proteins. Liu’s team attaches the adapters to polymer fragments to produce macrocyclic building blocks. After polymer synthesis, the researchers cleave a disulfide linker to remove the adapter. They have made β-peptides and polyethylene glycol polymers of up to 26 kilodaltons, about the same mass as a 230-amino acid protein. The polymers are completely encoded by DNA and don’t require enzymes for production. The team now aims to adapt this system to evolve synthetic polymers with new or improved features, such as antibiotic activity.

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