Serge D. Zemerov

PhD Student and TCNJ Alum, UPenn

Wednesday, March 7, 2018
11:00 to 11:50 am
C – 121

Synthetic and genetically encoded biosensors and contrast agents for ultrasensitive ¹²⁹Xe NMR

Abstract:
Proton-based magnetic resonance imaging (¹H MRI) is a widely used technique for the detection and diagnosis of human disease states. However, it is poorly suited for imaging void spaces, due to its reliance on the proton signal from endogenous water and fat. Additionally, ¹H MRI experiments require high sample concentrations and/or long acquisition times due to the low sensitivity inherent in the technique, limiting its use in imaging low-abundance biomarkers. To overcome these issues, hyperpolarized ¹²⁹Xe NMR and MRI have been investigated as complements to ¹H-based techniques. In this talk, I will summarize our laboratory’s efforts to develop ¹²⁹Xe-based imaging as a complement to traditional ¹H MRI. Specifically, I will focus on the synthesis and characterization of the small organic Xe host molecules known as cryptophanes, as well as on our studies of genetically encoded (GE) ¹²⁹Xe NMR contrast agents. The chemical shift of¹²⁹Xe is highly sensitive to its chemical environment due to its large and polarizable electron cloud, which allows for the use of ¹²⁹Xe NMR to detect the binding of a functionalized cryptophane cage to various biomedically relevant proteins. Additionally, we have recently identified two proteins, TEM-1 β-lactamase and maltose binding protein, as potential GE xenon biosensors, which have the advantages of being expressed directly in the tissue of interest and tailored to bind specific analytes. These synthetic and GE biosensors offer exciting possibilities for advancing ultrasensitive detection of ions, small molecules, and proteins via¹²⁹Xe NMR/MRI.