Synthesis of a Potential FRET-Based Continuous Glucose Sensor Molecule

Abstract

For decades, millions of people have been suffering from diabetes. Common methods to monitor blood glucose levels include the use of finger stick glucose meters and test strips. Finger prick to draw blood sample is required regularly and can be painful and annoying. Continuous blood glucose monitors (CGM) are commercially available however they still require calibration with a traditional blood glucose measurement and test results lag behind actual blood glucose values. The objective of this project is to develop an indicator molecule that can be potentially used for fluorescence-based continuous glucose sensors once inserted under skin. A scaffold structure was previously designed using the computer program CAVEAT. A simple structure corresponding to this scaffold was prepared that showed some selectivity for glucose and affinity in the proper range. Incorporation of donor and acceptor flurophores for fluorescence signaling derived the final structure. Once being bound to glucose, this structure would be locked in a conformation that holds the fluorophores about 20 ÌÉ apart. The extent of FRET between fluorophores would be greatly decreased hence providing a fluorescence signal for glucose binding. The synthesis of original designed FRET-based glucose sensor 7 encountered great difficulties. It was modified to 35 to make the synthesis easier. The synthesis of the modified FRET-based glucose sensor is under investigation.