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bioRxiv · 10.1101/500611

Electrostatic-assemblies of single-walled carbon nanotubes and sequence-tunable peptoid polymers detect a lectin protein and its target sugars

Chio, L.·Del Bonis-O'Donnell, J. T.·Kline, M.·Kim, J.-H.·McFarlane, I. R.·Zuckermann, R. N.·Landry, M.
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Abstract

A primary limitation to real-time imaging of metabolites and proteins has been the selective detection of biomolecules that have no naturally-occurring or stable molecular recognition counterparts. We present developments in the design of synthetic near-infrared fluorescent nanosensors based on the fluorescence modulation of single-walled carbon nanotubes (SWNT) with select sequences of surface-adsorbed N-substituted glycine peptoid polymers. We assess the stability of the peptoid-SWNT nanosensor candidates under variable ionic strengths, protease exposure, and cell culture media conditions, and find that the stability of peptoid-SWNTs depends on the composition and length of the peptoid polymer. From our library, we identify a peptoid-SWNT assembly that can selectively detect lectin protein wheat germ agglutinin (WGA) with a sensitivity comparable to the concentration of serum proteins. This WGA protein nanosensor is characterized with near-infrared spectroscopy and microscopy to study protein-nanosensor interaction parameters. To demonstrate the retention of nanosensor-bound protein activity, we show that WGA on the nanosensor produces an additional fluorescent signal modulation upon exposure to the lectins conjugate sugars, suggesting the lectin protein selectively binds its target sugars through ternary molecular recognition interactions relayed to the nanosensor. Our results inform design considerations for developing synthetic molecular recognition elements by assembling peptoid polymers on SWNTs, and also demonstrate these assemblies can serve as optical nanosensors for lectin proteins and their target sugars. Together, these data suggest certain peptoid sequences can be assembled with SWNTs to serve as versatile optical probes to detect proteins and their molecular substrates.

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Chio, L., Del Bonis-O'Donnell, J. T., Kline, M., Kim, J.-H., McFarlane, I. R., Zuckermann, R. N., Landry, M.. 2018-12-20. Electrostatic-assemblies of single-walled carbon nanotubes and sequence-tunable peptoid polymers detect a lectin protein and its target sugars. https://doi.org/10.1101/500611

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