The goal of this project is to develop a fluorescence-based sensor for glucose that may be used for the continuous monitoring of blood glucose levels in diabetes patients. This project is based on previous observations that the fluorescence of an arylboronic acid may be altered upon formation of a complex with glucose. While the change in fluorescence can be used to determine glucose concentration in solution, it is not specific for glucose as other sugars and related compounds can also induce the fluorescence change. The goal of this project is to develop new methods for building in high selectivity for complex formation with glucose in systems chosen such that the extent of glucose binding can be conveniently determined by fluorescence measurements. This will provide the basis for a practical sensor for the measurement of glucose concentration in the presence of a variety of sugars and other potential interfering substances. The design of specific glucose receptors will be based on computer-aided design of molecular structures that permit the precise positioning of multiple functional groups that will bind to different parts of a glucose molecule. Structures designed by this approach will be synthesized and the binding of glucose and accompanying fluorescence changes will be studied. Initial structures will be further modified to tune the sensor to physiological glucose concentration and other practical issues in glucose sensor development will be addressed.
| Ballou, Lisa M; Selinger, Elzbieta S; Choi, Jun Yong et al. (2007) Inhibition of mammalian target of rapamycin signaling by 2-(morpholin-1-yl)pyrimido[2,1-alpha]isoquinolin-4-one. J Biol Chem 282:24463-70 |
