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Designing nanosensors based on ion channel-forming derivatives of Gramicidin A

Abstract

This dissertation will focus on detecting analytes in aqueous solution that chemically react with or bind to functional groups near the opening of synthetic ion channels derived from gramicidin A (gA). Detection is achieved when a measurable change in the conductance of ions across the ion channel is produced after the analyte interacts with the channel. Ion channel sensors have great potential for achieving ultrasensitive detection since a single chemical modification near the lumen of the channel can lead to detectable changes in channel conductance. The dissertation will specifically focus on: (1) the development of design parameters to improve sensing with gA-based nanosensors; (2) the demonstration of sensing analytes in aqueous solution by manipulating the charge of a chemical group near the pore of gA (charge-based sensing); (3) the chemistry for producing reactive building blocks of gA for developing robust and diverse gA -based nanosensors; (4) the detection of enzyme activity using our charge-based sensing approach to achieve picomolar limits of detection; and (5) the small structural changes that can be introduced to the peptide near the lumen of the channel to control conductance

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