PMID: 11899062Mar 20, 2002Paper

Miniaturized formats for efficient mass spectrometry-based proteomics and therapeutic development

Current Topics in Medicinal Chemistry
Gary A Valaskovic, Neil L Kelleher

Abstract

Off-line miniaturized "nano-spray" formats for electrospray ionization mass spectrometry (ESI-MS) enable the routine identification of femtomole quantities of protein or peptide. Even greater strides have been achieved using on-line miniaturized ESI-MS methods, such as nanobore LC-MS and CE-MS. On-line methods enable greater sensitivity (sub-attomole limit of detection), dynamic range, and throughput. In either off- or on-line methods for protein analysis, samples are typically isolated and digested enzymatically, with MS analysis of the peptide fragments, yielding 5-50% sequence coverage, in a "bottom-up" approach. Obtaining biologically relevant (structure/function) information (such as the localization of regions of error or post-transnational modifications) often demands 100% sequence coverage and this may be obtained by analyzing intact proteins by MS with a "top-down" methodology. Proteome wide success with top-down methods will require the development of novel miniaturized approaches for sample preparation along with new tools for bioinformatics. As these miniaturized formats continue to power proteomics applications, they will undoubtedly pollinate "cross-over" applications in LC-MS ranging from drug discovery to develo...Continue Reading

Citations

Dec 4, 2004·Analytical and Bioanalytical Chemistry·Harald John
Dec 19, 2015·Journal of Proteome Research·Fei LiuMark S Baker
Apr 1, 2006·Drug Discovery Today. Technologies·Georges L Gauthier, Rudolf Grimm
Nov 18, 2014·Biochemical Society Transactions·Robert J BeynonYvonne Woolerton
Mar 12, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Nik Soriani YaacobMohd Nor Norazmi
Aug 27, 2014·Bioanalysis·Michael E Lassman, Carmen Fernandez-Metzler
Jun 2, 2016·Cell Cycle·Tianzhou ZhangMichael Leitges
Oct 1, 2005·Proteomics·Joerg Reinders, Albert Sickmann
Nov 18, 2010·Journal of Medicinal Chemistry·Niamh M O'BoyleMary J Meegan
Nov 5, 2014·Journal of Medicinal Chemistry·Niamh M O'BoyleMary J Meegan

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