Document Type

Honors Thesis

Degree Name

Bachelor in Chemistry

Date of Award

Spring 5-31-2013

Abstract

Insulin is a hormone protein essential to the regulation of blood sugar levels. Although it is active as a hormone in the monomer (single insulin unit) form, it is stored in the pancreas as a hexamer – a coordination of six insulin units and zinc ions. This research analyzes the effects of zinc ions on the formation, stability, and fragmentation of the hexamer and other oligomer species in varying solution and instrument conditions, including the ability of the higher oligomers to transfer from crystallization to solution to a gas phase for analysis using electrospray ionization ion mobility mass spectrometry (ESI-IM-MS). Studying the conformation and stability of its active monomer, storage hexamer, and intermediate aggregated forms will enable the further understanding of the protein and open up the potential for the improvement of drugs and oligomeric protein analysis. Using ESI-IM-MS, the oligomers of insulin were separated and more accurately identified than through quadrupole time-of-flight (QTOF) mass spectrometry, which results in “hidden” low intensity species. Novel species observed through ESI techniques included trimer and pentamers of multiple charges. The oligomers were fragmented through collision induced dissociation (CID) in both traditional QTOF and IM modes. Unexpected relative stabilities and novel patterns of fragmentation were observed and analyzed.

Advisor

Laurence Angel

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