Doctor of Philosophy (PhD)
Reliable and selective detection of specific biopolymers is critical in a broad range of biomedical and technological areas, including availability of simple and efficient point-of-care-compatible systems for the detection of prognostic, pharmacodynamic and predictive biomarkers. Monitoring epidermal growth factor receptor (EGFR) tyrosine kinase is of major significance due to its link to many epithelial cancers. This task is complicated by the high rate of mutation occurring in patients treated with kinase inhibitors. This dissertation describes a conceptually novel design and synthesis of turn-on near-infrared fluorescent sensors for selective and sensitive detection of EGFR. The fluorescent signal generation mechanism is based on the aggregation/de-aggregation of phthalocyanine chromophores controlled by selective binding of small-molecule “anchor” groups to a specific binding site of a target biopolymer. Due to universality of the signal generation mechanism, and the response selectivity independently coming from a proper choice of a small-molecule “anchor” group, this approach can offer broad capabilities in designing turn-on fluorescent sensors for EGFR kinase as well as for various other protein targets, and facilitate use of this system in point-of-care centers in order to decrease monetary and time cost of treatment for the patients.
Ducharme, Gerard Thomas, "Turn-On Near-Infrared Fluorescent Sensors for Selective Monitoring of Kinase Activity" (2019). LSU Doctoral Dissertations. 5055.