Oddball enzyme provides easy path to synthetic biomaterials

The molecular machinery of the human body typically relies on genetic templates to carry out construction. For example, molecular machines called DNA polymerases read DNA base-by-base to build accurate copies.

There are, however, a few black sheep in the world of molecular biology that do not require a template. One such outlier, called terminal deoxynucleotidyl transferase (TdT), works in the immune system and catalyzes the template-free addition of nucleotides — the building blocks of DNA — to a single-stranded DNA.

Seemingly random nucleotide sequences in a single DNA strand wouldn’t seem to have much of a biological use — but materials scientists have figured out what to do with it.

In a new paper, Duke University researchers build on their previous work and now describe in detail how the TdT enzyme can produce precise, high molecular weight, synthetic biomolecular structures much more easily than current methods. Researchers can tailor synthesis to create single-stranded DNA that self-assemble into ball-like containers for drug delivery or to incorporate unnatural nucleotides to provide access to a wide range of medically useful abilities.

The results appear online on May 15, 2017 in the journal Angewandte Chemie International Edition.

“We’re the first to show how TdT can build highly controlled single strands of DNA that can self-assemble into larger structures,” said Stefan Zauscher, the Sternberg Family Professor of Mechanical Engineering and Materials Science at Duke University. “Similar materials can already be made, but the process is long and complicated, requiring multiple reactions. We can do it in a fraction of the time in a single pot.”

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