Antibody-Mimetic Protein Detection with Peptoid-Functionalized Near-Infrared Carbon Nanotube Optical Sensors (Award Submission)

A primary limitation to real-time imaging of small molecule metabolites and proteins has been the selective detection of biomolecules that have no naturally-occurring molecular recognition counterpart. We present recent developments in the design of synthetic near-infrared and non-photobleaching fluorescent sensors, ‘synthetic antibodies’, to detect such protein analytes, based on the fluorescence modulation of single-walled carbon nanotubes (SWNT). Using bio-mimetic loop-displaying peptoids, or N-substituted glycine, polymers, we have created a peptoid-SWNT sensor that is sensitive and selective for the lectin protein wheat germ agglutinin. We show the sensitivity of this sensor to be comparable to the concentration of serum proteins. The protein sensor is further characterized using near-infrared spectral and microscopy studies to extract protein-sensor interaction parameters, kinetic binding constants, and ternary selective interactions of the lectin with its conjugate sugar. This peptoid-SWNT sensor is the first example of a synthetic peptoid-nanoparticle biosensor with sugar recognition, and informs us of design considerations for developing synthetic molecular recognition elements to detect proteins and complex biomolecules.