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Author ORCID Identifier

https://orcid.org/0000-0002-1882-3182

AccessType

Open Access Dissertation

Document Type

dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Chemistry

Year Degree Awarded

2019

Month Degree Awarded

September

First Advisor

Richard W. Vachet

Second Advisor

S. Thayumanavan

Subject Categories

Amino Acids, Peptides, and Proteins | Analytical Chemistry | Biomedical and Dental Materials | Investigative Techniques | Materials Chemistry | Organic Chemistry | Other Analytical, Diagnostic and Therapeutic Techniques and Equipment | Other Biochemistry, Biophysics, and Structural Biology | Polymer Chemistry

Abstract

Mass spectrometry (MS) has played an increasingly prominent role in proteomics and structure biology because it shows superior capabilities in identification, quantification and structural characterization of proteins. To realize its full potential in protein analysis, significant progress has been made in developing innovative techniques and reagents that can couple to MS detection. This dissertation demonstrates the use of polymeric supramolecular assemblies for enhanced protein detection in complex biological mixtures by MS. An amphiphilic random co-polymer scaffold is developed to form functional supramolecular assemblies for protein/ peptide enrichment. The influences of charge density and functional group pKa on host-guest interactions within the assemblies are fundamentally investigated. In practice, these new materials enable specific isolation of target peptides from complex mixtures, as well as enhance MS detection/ quantification of protein biomarker in human breast milk. In parallel to protein detection, this dissertation also describes the development of a series of small-molecule covalent labeling (CL) reagents that are capable of studying protein higher order structure and protein-protein interactions when coupled with MS.

DOI

https://doi.org/10.7275/14726272

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