New biosensing strategies using hyperpolarized xenon-129 NMR spectroscopy / Yanfei Wang.

Format:

Book

Manuscript

Thesis/Dissertation

Author/Creator:

Wang, Yanfei, author.

Contributor:

Dmochowski, Ivan J., degree supervisor.

Saven, Jeffery G., degree committee member.

Baumgart, Tobias, degree committee member.

Christianson, David W., degree committee member.

University of Pennsylvania. Department of Chemistry, degree granting institution.

Language:

English

Subjects (All):

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

Local Subjects:

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

Physical Description:

xv 179 leaves : illustrations ; 29 cm

Production:

[Philadelphia, Pennsylvania] : University of Pennsylvania, 2016.

Summary:

Molecular imaging holds considerable promise for elucidating biological processes in normal physiology as well as disease states, by determining the location and relative concentration of specific molecules of interest. Proton-based magnetic resonance imaging (1H MRI) is non-ionizing and provides good spatial resolution for clinical imaging, but lacks sensitivity for imaging low-abundance (i.e., submicromolar) molecular markers of disease, or environments with low proton densities. To address these limitations, hyperpolarized 129Xe NMR spectroscopy and MRI have emerged as attractive complementary methodologies. Beyond hyperpolarization, a 107-fold signal enhancement can be achieved by using novel indirect detection schemes (namely, Hyper-CEST), showing great potential to meet the sensitivity requirement in many applications.

The concept of using 129Xe NMR for biosensing was first proposed by a Berkeley team in 2001 to realize targeted imaging and biological sensing at a molecular level. The development of xenon biosensors has since focused on modifying organic host molecules (e.g., cryptophanes) via diverse conjugation chemistries, and has brought about numerous sensing applications including detection of chemical modifications, oligonucleotide hybridization, enzyme active-site binding or enzyme-mediated proteolysis, and peptide binding events. Designs for new 129Xe NMR biosensors have recently extended beyond cryptophanes to new xenon-interacting scaffolds.

The expanded palette of 129Xe NMR biosensors now includes synthetic cryptophane and cucurbit[6]uril constructs, as well as genetically-encoded gas vesicles and single proteins. In 2015 our lab first reported the Hyper-CEST capability of cucurbit[6]uril, and this molecule has received additional attention in the past year due to its commercial availability and excellent Hyper-CEST response. The 'turn-on' strategy reported by both our lab and Pines provided a desirable alternative approach for biosensing. We also recently demonstrated that TEM-1 β-lactamase can function as a single-protein reporter for hyperpolarized 129Xe NMR, and observed useful saturation contrast for β-lactamase expressed in bacterial cells and mammalian cells. These newly developed biosensors promise great potential in extending the scope of hyperpolarized 129Xe imaging towards molecular MRI, and efforts I made in these studies will be discussed in this thesis.

Notes:

Ph. D. University of Pennsylvania 2016.

Department: Chemistry.

Supervisor: Ivan J. Dmochowski.

Includes bibliographical references.

OCLC:

970617004