New Library of Artificial Antibodies Could Target Pathogens With Molecular Precision

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Computer simulation of an anthrax PA63 protein binding to loopoids (purple). The base nanosheet is shown in green. (Credit: Ryan Spencer and Ron Zuckermann/Berkeley Lab).

A research team led by Berkeley Lab has developed a technique that could accelerate the design of artificial antibodies for biomedical applications – from sensing technologies that detect and neutralize infectious viruses and bacteria to the early detection of Alzheimer’s.

Antibodies are proteins in the body’s immune system that defend the body against infection by pathogens, such as viruses and bacteria. Unfortunately, antibodies are expensive to manufacture and challenging to store.

Now, as reported in the journal ACS Nano, scientists at Berkeley Lab have designed artificial antibodies that rival the chemical diversity of their natural counterparts, but without their fragility, nor the expense.

Ron Zuckermann of Berkeley Lab’s Molecular Foundry and his co-authors engineered a family of protein-like molecules called peptoids to fold into a nanosheet coated with peptoid loops – what the researchers call “loopoids.” While the peptoids direct the formation of the nanosheet, the loopoids create libraries of chemically diverse 2D surfaces that can be tested for biological activity, Zuckermann explained.

The density of loops on the nanosheet offers multiple sites that can simultaneously attach to pathogens, boosting their binding strength. Because of their high surface area, a single nanosheet can bind thousands upon thousands of target proteins, and can even grab onto much larger biological targets like bacterial cells.

While testing the technique, the researchers identified a peptoid nanosheet that selectively binds to a key protein involved in the interaction between the anthrax pathogen and its host cell.

We can now readily build populations of rugged synthetic materials that can be engineered to recognize a potential pathogen,” said Zuckermann. “It is a shining example of biomimetic nanoscience.”

Researchers from UC San Francisco, New York University, and Pacific Northwest National Laboratory also participated in the work.

Source: Theresa Duque at Berkeley Lab

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