Mass Spectrometry OMICS Approach to Study Medicinal Chemical Molecular Responses on Living Organisms

Abstract

Studies on the effect of drugs on organisms such as plants, animals and human beings have experienced an evolutionary leap in the form of proteomic and metabolomic analysis using mass spectrometry (MS). The 2002, Chemistry Nobel prize winner John Fenn established a landmark in this field by introducing the electrospray ionization technique (ESI), which allows for the transfer of proteins and small biomolecules from solutions to mass spe`ctrometers for MS analysis [1,2]. Since the advent of ESI-MS, a great variety of methodologies have appeared to help scientists in solving important questions on clinical and medicinal chemistry. MS has been now established as the stateof-the-art analytical tool in which richest data from molecular systems can be acquired. In medicinal chemistry, three MS approaches might be highlighted as the most prominent: data dependent UPLC-ESI-HRMS metabolomics [3], data dependent nanoLC-nanoESI-HRMS proteomics [4] and MS imaging applied to the biomarker screening of tissues [5].Metabolomic MS screening can usually be categorized into untargeted [6] and targeted analysis [7]. In untargeted metabolomics, as many molecules as possible are identified in a sample. Relative quantities of analytes can be determined when comparing treatments. Targeted metabolomics focuses on the relative or absolute quantitation of molecular targets using internal standards and/or analytical curves. Some MS approaches in metabolomic analysis have been interested in the identification of metabolites that are formed in vivo out of administered medication. The metabolism is directly related with both toxic effects and activity. Another field on interest in metabolomics is the study of how the regular metabolism of organisms is influenced by an administered medication.The metabolic approach uses both high volume data obtained from chromatographic separation, as well as high-resolution MS data. These accurate data provide information of molecular formulas with errors around 1 ppm. Due to the high velocity of MS acquisition, tandem MS data from target constituents can be used to increase identification accuracy of thousands of small molecules in just one analytical run. This MS/MS data facilitates in the formation of an overview of present molecules per sample. Data handling using PCA or PLS statistical approaches is used to relate treatment evaluation with metabolite up and down regulation. For selectivity improvement in metabolomics, MS coupled to ion-mobility mass spectrometry can be used, in which molecules are separated according to their shape and then characterized even more reliably allowing the discrimination between isomeric or isobaric metabolites.Proteomics analysis is currently conducted using nanoLCnanoESI-HRMS. It is therefore expected that this technique will soon be applied to the analysis of living organisms. The correlation of the proteome with metabolomics could be seen as the Holy Grail of how living organisms' work by being able to gather information that combines genomics-proteomics-metabolomics a...