Identifier

etd-03132015-132345

Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

This work involves the investigation of a group of uniform materials based on organic salts (GUMBOS) as matrices for matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF) for analysis of hydrophobic biomolecules. GUMBOS are new class of materials that show great promise as MALDI matrices because they are able to form a thin-layer on the MS target, thereby enhancing the sample homogeneity, signal intensity, and shot-to-shot reproducibility. The detection of hydrophobic peptides using MALDI-TOF MS remains a challenge because the majority of matrices utilized are hydrophilic thereby exhibiting low affinity for hydrophobic molecules. To address this, I have developed novel matrices of varying hydrophobicity based on aminopyrine (AP) to enhance the detection of such molecules. In the first part of this work, I outline the synthesis of a series of AP-based GUMBOS in which various counter-ions such as chloride, ascorbate, and bis(trifluoromethane) sulfonamide were used to tune the hydrophobicity of a matrix. The hydrophobicities of these compounds relative to á-cyano-4-hydroxycinnamic acid (CHCA), a common MALDI matrix, indicated that the AP-based GUMBOS can be tuned to greater hydrophobicity than CHCA. In addition, a clear trend was observed between the signal intensity of the hydrophobic peptides and the hydrophobicity of the matrix. In the second part of this work, I present a unique approach for predicting matrix-analyte interactions in MALDI using fluorescence spectroscopy. Interactions of analytes with matrices that are composed of AP and AP-based GUMBOS were investigated using a hydrophobic (gramicidin) and a hydrophilic peptide (angiotensin II). Fluorescence anisotropy and Scatchard analysis were used to investigate the interaction between matrices and peptides. Hydrophobic AP and AP-based GUMBOS revealed stronger interactions with hydrophobic peptides and enhanced detection of these peptides, which correlate well with the MALDI MS results. Finally, I have synthesized a hydrophobic GUMBOS-based matrix using CHCA and oleylamine (OA). The [OA][CHCA] GUMBOS was used as a matrix for MALDI MS for the detection of lipids in tissues and compared with 2,5-dihydroxybenzoic acid (DHB) had better signal reproducibility and improved homogeneity. These enhancements were used to examine the distribution and localization of different classes of lipids in tissue.

Date

2015

Document Availability at the Time of Submission

Secure the entire work for patent and/or proprietary purposes for a period of one year. Student has submitted appropriate documentation which states: During this period the copyright owner also agrees not to exercise her/his ownership rights, including public use in works, without prior authorization from LSU. At the end of the one year period, either we or LSU may request an automatic extension for one additional year. At the end of the one year secure period (or its extension, if such is requested), the work will be released for access worldwide.

Committee Chair

Warner, Isiah

Included in

Chemistry Commons

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