HIGH RESOLUTION MASS SPECTROMETRIC STRATEGIES FOR DETECTION OF PROTEINS AND PEPTIDES COVALENTLY MODIFIED BY ELECTROPHILIC XENOBIOTICS AND ENDOGENOUS INTERMEDIATES
Tesi di Dottorato
Data di Pubblicazione:
2015
Citazione:
HIGH RESOLUTION MASS SPECTROMETRIC STRATEGIES FOR DETECTION OF PROTEINS AND PEPTIDES COVALENTLY MODIFIED BY ELECTROPHILIC XENOBIOTICS AND ENDOGENOUS INTERMEDIATES / D. Garzon ; ALDINI GIANCARLO, VALOTI ERMANNO. Università degli Studi di Milano, 2015 Jan 15. 27. ciclo, Anno Accademico 2014. [10.13130/garzon-davide_phd2014].
Abstract:
Non enzymatic protein covalent modifications are involved in the toxic effects induced by electrophilic xenobiotics as well as by endogenous cytotoxic oxidation by-products. Aim of my Ph.D work was to set-up MS methods for the identification, characterization and quantification of non-enzymatic covalently modified proteins and peptides in biological matrices. To reach this goal both tandem MS and high resolution approaches were employed due to the wealth of structural and molecular information that these techniques can provide.
As a first step the MS methods were applied for understanding in both in vitro and ex vivo conditions the mechanism of protein haptenation induced by amoxicillin (AX). The MS approach was then focused to study in ex vivo condition the covalent reaction between histidine dipeptides, such as carnosine, and toxic endogenous intermediates like reactive carbonyl species (RCS).
.
Tipologia IRIS:
Tesi di dottorato
Keywords:
mass spectrometry; HPLC; nano LC; protein covalent modification; amoxicillin; protein haptenation; allergic drug reactions; ex vivo samples; reactive carbonyl species; Carnosine; intervention study; RCS detoxfication agents; Advanced Glycation End Products (AGEs); Advanced Lipoxidation End Products (ALEs)
Elenco autori:
D. Garzon
Link alla scheda completa:
Link al Full Text: