Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Chemistry

First Advisor's Name

Francisco Fernandez-Lima

First Advisor's Committee Title

Co-Committee chair

Second Advisor's Name

Yuk-Ching Tse-Dinh

Second Advisor's Committee Title

Co-Committee chair

Third Advisor's Name

Fenfei Leng

Third Advisor's Committee Title

Committee member

Fourth Advisor's Name

Jessica Siltberg-Liberles

Fourth Advisor's Committee Title

Committee member

Fifth Advisor's Name

Yuan Liu

Fifth Advisor's Committee Title

Committee member

Keywords

Trapped IOn Mobility Spectrometry, Mass Spectrometry, DNA complexes

Date of Defense

3-26-2018

Abstract

The characterization of biomolecules and biomolecular complexes represents an area of significant research activity because of the link between structure and function. Drug development relies on structural information in order to target certain domains. Many traditional biochemical techniques, however, are limited by their ability to characterize only certain stable forms of a molecule. As a result, multidimensional approaches, such as ion mobility mass spectrometry coupled to mass spectrometry (IMS-MS), are becoming very attractive tools as they provide fast separation, detection and identification of molecules, in addition to providing three-dimensional shape for structural elucidation. The present work expands the use and application of trapped ion mobility spectrometry-coupled to mass spectrometry (TIMS-MS) by analyzing a range of biomolecules (including proteoforms, intrinsically disordered peptides, DNA and molecular complexes). The aim is to i) evaluate the TIMS platform measuring sensitivity, selectivity, and separation of targeted compounds, ii) pioneer new applications of TIMS for a more efficient and higher throughput methodologies for identification and characterization of biomolecular ions, and iii) characterize the dynamics of selected biomolecules for insight into the folding pathways and the intra-or intermolecular interactions that define their conformational space.

Identifier

FIDC004097

Available for download on Saturday, October 27, 2018

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