Targeted proteomics in biomarker validation: detection and quantification of proteins using a multi-dimensional peptide separation strategy

Proteomics
Dorian ImmlerPeter Reinemer

Abstract

Authentic biomarkers, distilling the essence of a complex, functionally significant process in a mammalian system into a precise, physicochemical measurement have been implicated as a tool of increasing importance for drug discovery and development. However, even in spite of recent technological advances, validating a new biomarker candidate, where generation of suitable antibodies is required, is still a long-lasting task. Methods to accelerate initial validation by MS approaches have been suggested, but all methods described so far are associated with serious drawbacks, finally leading to non-generic methods of detection and quantification. Moreover, when complex body fluids are used as samples, efficient debulking strategies are crucial to open a window of analytical sensitivity in the ng/mL range, where many diagnostically relevant analytes are present. Here we report the proof-of-principle of a multi-dimensional strategy for accelerated initial validation of biomarker candidates by MS, which promises to be generally applicable, sensitive and quantitative. The method presented employs a combination of electrophoretic and chromatographic steps on the peptide level, followed by MS quantification using isotopically labeled syn...Continue Reading

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Citations

Jun 11, 2008·Molecular & Cellular Proteomics : MCP·Stefan HellingBernhard Kadenbach
Mar 31, 2010·Bioanalysis·Eugene Ciccimaro, Ian A Blair
Aug 23, 2011·Journal of Proteomics·Jinong LiZivana Tezak
Dec 19, 2015·Journal of Proteome Research·Fei LiuMark S Baker
Feb 1, 2008·Proteomics. Clinical Applications·Kothandaraman NarasimhanMahesh Choolani
Nov 6, 2008·Rapid Communications in Mass Spectrometry : RCM·Benjamin MannMilos V Novotny
Sep 1, 2011·Mass Spectrometry Reviews·Peihong ZhuJohn G Marshall
Aug 5, 2008·Bioorganicheskaia khimiia·Iu V SungurovS A Semenova
Feb 1, 2009·Proteomics. Clinical Applications·Deborah Penque
Jul 26, 2007·Chemical Reviews·Marjorie L FournierMichael P Washburn

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