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Synthesis of matrices for MALDI spectrometry
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
2021 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Parkinson's disease (PD) is a neurodegenerative disease characterized by a disorder in the cells that produce dopamine. It mostly affects people older than 60 years old and more common for men than women. Disturbances in these signal transmissions lead to progressive motor impairment such as reduced mobility, dyskinesia, and tremors. 

Matrix-assisted laser desorption ionization (MALDI) has become one of the most important "soft" mass spectrometry methods to analyze macromolecules such as proteins, polymers, lipids, and peptides in tissue. MALDI is a suitable method for label-free mapping of molecules in tissue samples found in the brain and lung slices. Several research questions can be explored in Parkinson's diseases using MALDI MS to analyze the localization of new PD drugs in the brain. 

In MALDI MS, the choice of the matrix has a major role in the detection of the analyte. The matrix has the function of absorbing the laser UV light, which protects the integrity of the analysis and helps ionization. Important matrix properties include the ability to absorb the specific wavelength from the laser, maintain stability under vacuum conditions, analyte ionization, and prevent the formation of cluster ions. There are two types of matrices, regular and reactive matrices and recent development has a strong focus on reactive matrices because of their advantages in small molecule detection. 

 

The purpose of this work to increase sensitivity in MALDI MS by synthesizing three matrices that can either react with carbonyl, aldehyde, or alkene. The matrices were synthesized by using Suzuki coupling reaction, Wittig reaction and methylation. The purpose of this work was achieved, and the three matrices have been synthesized and purified for testing in MALDI MS. 

 The result from MALDI MS will show if these matrices have resolved the problem of low sensitivity. And another possible future work is to test the Wittig reaction on the ketone product to compare this one to aldehyde.

 

 

 

Place, publisher, year, edition, pages
2021.
National Category
Medicinal Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-451978OAI: oai:DiVA.org:uu-451978DiVA, id: diva2:1590162
Educational program
Master of Science Programme in Pharmacy
Supervisors
Examiners
Available from: 2023-03-20 Created: 2021-09-01 Last updated: 2023-03-20Bibliographically approved

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