Abstract
In the modern process of drug discovery, clinical, functional and chemical proteomics can converge and integrate synergies. Functional proteomics explores and elucidates the components of pathways and their interactions which, when deregulated, lead to a disease condition. This knowledge allows the design of strategies to target multiple pathways with combinations of pathway-specific drugs, which might increase chances of success and reduce the occurrence of drug resistance. Chemical proteomics, by analyzing the drug interactome, strongly contributes to accelerate the process of new druggable targets discovery. In the research area of clinical proteomics, proteome and peptidome mass spectrometry-profiling of human bodily fluid (plasma, serum, urine and so on), as well as of tissue and of cells, represents a promising tool for novel biomarker and eventually new druggable targets discovery. In the present review we provide a survey of current strategies of functional, chemical and clinical proteomics. Major issues will be presented for proteomic technologies used for the discovery of biomarkers for early disease diagnosis and identification of new drug targets.
Highlights
Over the past few years, mass spectrometry (MS)-based proteomics has expanded its interface role to the broad and diverse research areas of science and technology [1,2,3]
MALDI-TOF MS-based approaches for profiling clinical samples. This strategy may appear as a direct avenue for biomarker discovery because it consists in the direct analysis of low molecular weight metabolites, endogenous peptides and proteins in readily accessible bodily fluids or, more difficult to obtain, in sample tissues
Chemical proteomics strategies aiming at the comprehension of drug interactome can contribute to optimization of lead compounds improving drug selectivity and specificity, reducing side effects
Summary
Over the past few years, mass spectrometry (MS)-based proteomics has expanded its interface role to the broad and diverse research areas of science and technology [1,2,3]. MS has greatly implemented quantitation issues [5] These efforts have provided a powerful tool to assess qualitative-quantitative differences in protein profiles of different samples, in particular diseased vs normal. Proteomic approaches have been increasingly applied to the study of clinical samples, such as cell lysates, tissues or body fluids, with the purpose of discovering novel disease-specific protein biomarkers. By assessing protein expression profiles and post-translational modifications (PTMs) in healthy and diseased, or drug-treated samples, clinical proteomics has the potential to discover, identify and quantify novel biomarkers to facilitate the early detection, diagnosis and therapeutic intervention of disease. The power of MS-based functional proteomics has allowed the characterization of cellular, subcellular or organismal proteins providing significant insight into cell biological processes and signal transduction pathways which are at the basis of the drug discovery [7,8,9]. In the complex drug discovery scenario, the various MS-based proteomic approaches extend beyond the common objective of drug target discovery, enabling the study of drug-target interaction (selectivity and specificity), drug activity (efficacy, resistance, toxicity) and elucidating the mechanism of action of a drug
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