Glycobiology is poised to be the next revolution in biology and medicine; however, technical difficulties in detecting and characterizing glycans prevent many biologists from entering this field, thus hampering new discoveries and innovations. Herein, we propose developing a conceptually novel technology that will allow straightforward identification of specific glycosylation patterns in biofluids and in live cells. Distinct glycosylation states will be differentiated by developing “artificial noses” in the size of a single molecule, whereas selectivity toward particular glycoproteins will be obtained by attaching them to specific protein binders. To achieve high sensitivity and accuracy, several innovations in molecular recognition and fluorescence signalling are integrated into the design of these unconventional molecular analytical devices.
One of the most important motivations for developing these sensors lies in their potential to diagnose a variety of diseases in their early stages. For example, we describe ways by which prostate cancer could be rapidly and accurately detected by a simple blood test that analyzes the glycosylation profile of the prostate-specific antigen (PSA). Another exceptional feature of these molecular analytical devices is their ability to differentiate between glycosylation patterns of specific proteins in live cells. This will solve an immense challenge in analytical glycobiology and will allow one to study how glycosylation contributes to diverse cell-signalling pathways. Finally, in the context of molecular-scale analytical devices, the proposed methodology is exceptional. We will show how “artificial noses” can be designed to target nanometric objects (e.g. protein surfaces) and operate in confined microscopoic spaces (e.g. cells), which macroscopic arrays cannot address. Taken together, we expect that the proposed technology will break new ground in medical diagnosis, cell biology, and biosensing technologies.
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