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Metallomic Studies Using Electrospray Ionisation-Mass Spectrometry (ESI-MS)

Applicant Dyson Paul
Number 133788
Funding scheme R'EQUIP
Research institution Laboratoire de chimie organométallique et médicinale EPFL - SB - ISIC - LCOM
Institution of higher education EPF Lausanne - EPFL
Main discipline Inorganic Chemistry
Start/End 01.12.2010 - 31.12.2011
Approved amount 100'000.00
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All Disciplines (2)

Discipline
Inorganic Chemistry
Biochemistry

Keywords (5)

electrospray-ionisation; mass spectrometry; metallomics; proteomics; mechanistic studies

Lay Summary (English)

Lead
Lay summary

In the last few years, our group has studied and developed new anticancer drugs that contain are effective against primary tumours and metastasis where classical drugs such as cisplatin and other related drugs are ineffective. The biomolecular interactions of most drugs, from intravenous application to delivery to the cell and entry into specific organelles such as the nucleus, are largely unknown. This project aims to clarify the ambiguity surrounding these by mapping the protein-drug interactions that occur inside and outside the cell. The Electrospray Ionisation-Mass Spectrometer (ESI-MS) that we intend to purchase will become the central analytical tool that will allow us to investigate and delineate these processes. Thus, the equipment will be dedicated in the elucidation of the mode of action of drugs in complex biological systems.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Associated projects

Number Title Start Funding scheme
140865 Rational design of organo-ruthenium anticancer compounds with novel modes of action 01.04.2012 Project funding
130647 An Integrated Approach to Study the Molecular Mechanisms of Ruthenium-Based Antitumour Agents (D-A-CH/LAV) 01.01.2011 Project funding (special)

Abstract

Over the last decade, mass spectrometry has turned into an indispensable tool in metallomic and proteomic research. Especially electrospray-ionisation mass spectrometry (ESI-MS) coupled online to separation systems such as liquid chromatography has become a major tool for the analysis of com-plex biological samples thanks to its capability to identify a large number of analytes within a single run. Consequently, the technique has also been widely employed in anticancer metallodrug research to characterize binding sites in biomolecules such as oligonucleotides and proteins even in real world samples, providing information on the mode of action of novel pharmaceuticals. Also other research areas in medicinal chemistry such as the elucidation of mechanisms enabling metal cations and met-allodrugs to pass the blood-brain-barrier, important for the future design of novel drugs, can profit greatly from data obtained by ESI-MS. Furthermore, it can help in obtaining essential information on the ecotoxicity of novel materials such as metal-based nanoparticles by analysing their fate upon interacting with microorganisms and bacteria.But ESI-MS does not only find application in biology-related research areas, it can also be applied to establish mechanistic level catalytic cycles for transition metal-based catalysts as used e.g. for the generation of hydrogen gas from formic acid to be used in environmental friendly fuel cells, making it a truly versatile tool in various areas of chemical research. Therefore, we apply for funding of a state-of-the-art ESI-MS instrument to extend ongoing projects and to initiate new research directions based on the profound experience in using this type of equipment at LCOM.
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