Researchers at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory have developed sugar-coated ultrathin self-assembling nanosheets that can selectively bind to pathogens, and which have potential to serve as a diagnostic technology or a way to inactivate pathogens.
The researchers developed the structures using bioinspired synthetic polymers, known as peptoids, which can self-assemble to form ultrathin nanosheets. “The chemical information that instructs the molecules to spontaneously assemble into the sugar-coated sheets is programmed into each molecule during its synthesis,” said Ronald Zuckermann, a researcher involved the study. “This work demonstrates our ability to readily engineer sophisticated biomimetic nanostructures by direct control of the polymer sequence.”
By patterning the surface of the nanosheets with simple sugars, which can selectively bind to specific proteins, the research team created a “designer fly paper” for a variety of pathogens. The outside of human cells is also covered in sugars, making the nanosheets a mimic of natural cell surfaces.
A 3-D-printed model of a peptoid nanosheet, showing patterned rows of sugars.
“It’s not just a ‘lock and key’ – it’s like Velcro, with a bunch of little loops that converge on the target protein together,” said Zuckermann. “Now we can mimic a nanoscale feature that is ubiquitous in biology.”
The researchers demonstrated that the nanosheets could selectively bind to a protein associated with the Shiga toxin, which causes dysentery. However, a variety of pathogens, including viruses and bacteria, naturally bind to sugars present on cell membranes, meaning that the nanosheets are customizable for a large array of applications, simply through adding the appropriate sugars.
“The chemistry we’re doing is very modular,” said Zuckermann. “We can ‘click on’ different sugars, and present them on a well-defined, planar surface. We can control how far apart they are from each other. We can do this with pretty much any sugar.”
The researchers envisage that the nanosheets could be used in preventative therapeutics, such as a nasal spray that someone could use to help prevent them becoming infected by a specific pathogen, such as the flu.
Study in ACS Nano: Glycosylated Peptoid Nanosheets as a Multivalent Scaffold for Protein Recognition
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