RT Journal Article SR Electronic T1 Electrostatic-assemblies of single-walled carbon nanotubes and sequence-tunable peptoid polymers detect a lectin protein and its target sugars JF bioRxiv FD Cold Spring Harbor Laboratory SP 500611 DO 10.1101/500611 A1 Linda Chio A1 Jackson Travis Del Bonis-O’Donnell A1 Mark A. Kline A1 Jae Hong Kim A1 Ian R. McFarlane A1 Ronald N. Zuckermann A1 Markita P. Landry YR 2018 UL http://biorxiv.org/content/early/2018/12/20/500611.abstract AB 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 lectin’s 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.