Combinatorial
Chemistry & High Throughput Screening
ISSN: 1386-2073
Combinatorial Chemistry &
High Throughput Screening
Volume 12, Number 2, February 2009
Contents
New Frontiers in Biological Mass Spectrometry
Guest Editor: Francesco L. Brancia
Editorial Pp. 124
Aspects of the Role of Surfaces in Ionization Processes
Pp. 125-136
Sara Crotti and Pietro Traldi
[Abstract]
[Purchase
Article]
[PMID:
19199882 PubMed - indexed for MEDLINE]
High-Energy Collision Induced Dissociation
of Biomolecules: MALDI-TOF/RTOF Mass Spectrometry in Comparison
to Tandem Sector Mass Spectrometry Pp. 137-155
Ernst Pittenauer and Günter
Allmaier
[Abstract]
[Purchase
Article]
[PMID:
19199883 PubMed - indexed for MEDLINE]
MALDI Mass Spectrometry Imaging, from
its Origins up to Today: The State of the Art Pp.
156-174
Simona Francese, Francesca R. Dani, Pietro
Traldi, Guido Mastrobuoni, Giuseppe Pieraccini and
Gloriano Moneti
[Abstract]
[Purchase
Article]
[PMID:
19199884 PubMed - indexed for MEDLINE]
The Effect of Post-Translational and
Process-Induced Modifications on the Multistage Gas-Phase
Fragmentation Reactions of Protonated Peptides Pp.
175-184
Jennifer M. Froelich and Gavin
E. Reid
[Abstract]
[Purchase
Article]
[PMID:
19199885 PubMed - indexed for MEDLINE]
Offline and Online Liquid Chromatography
Mass Spectrometry in Quantitative Proteomics Pp.
185-193
Jessica Z. Bereszczak and Francesco
L. Brancia
[Abstract]
[Purchase
Article]
[PMID:
19199886 PubMed - indexed for MEDLINE]
Recent Developments in Proteome Informatics
for Mass Spectrometry Analysis Pp. 194-202
James C. Wright and Simon J. Hubbard
[Abstract]
[Purchase
Article]
[PMID:
19199887 PubMed - indexed for MEDLINE]
Using Electrospray Ionisation Mass Spectrometry
to Study Non-Covalent Interactions Pp. 203-211
Bryan J. McCullough and Simon J.
Gaskell
[Abstract]
[Purchase
Article]
[PMID:
19199888 PubMed - indexed for MEDLINE]
The Importance of Steroidomics in the
Study of Neurodegenerative Disease and Ageing Pp.
212-228
William J. Griffiths and Yuqin
Wang
[Abstract]
[Purchase
Article]
[PMID:
19199889 PubMed - indexed for MEDLINE]
Meet
the Guest Editor Pp. 229
Abstracts
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Editorial:
Although rooted in physics, today mass spectrometry
(MS) has become an irreplaceable tool for scientists to study
the mechanisms of elemental and molecular processes occurring
in nature. Due to novel MS configurations and ionisation methods,
the last two decades have witnessed rapid and extensive utilisation
of mass spectrometry for qualitative and quantitative purposes.
Among several research fields, combinatorial chemistry has
benefited from the latest MS developments by providing innovative
approaches for structural characterisation of library components.
However, the high sensitivity required to detect low abundance
biomolecular species together with the high mass accuracy/resolving
power necessary for enhancing selectivity in analysis still
represent major challenges for any new development in mass
spectrometry. In addition, advances in mass analysers and
hardware configurations together with novel ionisation methods
must also be followed by improvements in software at both
the control and processing levels. Only then, more robust
mass spectrometers with higher levels of automation and throughput
can be delivered.
Through the reviews appearing in this special issue of Combinatorial
Chemistry & High Throughput Screening, we summarise
the state-of-art of biological mass spectrometry.
This issue brings together scientific leaders in their disciplines
who approach the problems arising in mass spectrometry from
different perspectives and provides a clear picture of instrumentation
and applications in MS including advantages and limitations
for the analysis of biomolecules.
In the review by Sara Crotti and Pietro Traldi, principles
of the novel atmospheric pressure ionisation techniques DESI
and SACI are described including their relevance for drug
analysis and metabolic profiling. Recent developments in time-of-flight
(ToF) geometries for MALDI tandem mass spectrometry are reviewed
by Ernst Pittenauer and Gunter Allmaier highlighting the most
recent applications with various biomolecules. Simona Francese
and collaborators offer a thorough summary of MALDI profiling
and imaging mass spectrometry for biological tissue analysis.
The impact on peptide sequencing using gas-phase fragmentation
of post-translationally modified and derivatized peptides
during multistage tandem mass spectrometry are addressed in
the review by Jennifer Froelich and Gavin Reid. Hyphenation
with liquid chromatography and the most recent developments
in micro/nanoliquid chromatography interfaced with MALDI and
electrospray ionisation for proteomics applications are discussed
in the review by Jessica Bereszczak and Francesco Brancia.
James Wright and Simon Hubbard summarise the current challenges
that bioinformatics must tackle due to the high volume of
complex data generated from large scale proteomics experiments.
The current mass spectrometry based methods in being used
to understand and characterise non-covalent protein complexes
by means of electrospray ionisation are discussed by Bryan
McCullogh and Simon Gaskell. Finally William Griffiths and
Yuqin Wang present an overview on steroidomics in the study
of neurodegenerative disease and ageing from a mass spectrometry
perspective.
As reported here, mass spectrometry is growing rapidly towards
new directions especially for peptide/protein analysis and
related research fields. This special issue provides a detailed
depiction of developments/applications in mass spectrometry,
which can subsequently be applied to enhance drug target identification.
Francesco L. Brancia
Shimadzu Research Laboratory
Trafford Wharf Road Wharfside
M17 1 GP, Manchester
UK
E-mail: francesco.brancia@srlab.co.uk
[Back to top]
[Purchase
Article] [PMID:
19199882 PubMed - indexed for MEDLINE]
Aspects of the Role of Surfaces in Ionization Processes
Sara Crotti and Pietro Traldi
The operating principles and some applications of atmospheric
pressure desorption electrospray ionization (DESI) and surface
activated chemical ionization (SACI) methods are described
in detail. The former technique allows one to obtain information
on the chemical composition (in terms of organic compounds)
present on a surface of interest. The latter, SACI, provides
chemical information as a result of the interaction of a vaporised
solution of the analyte with a metallic surface. Both techniques
typically lead to the production of abundant protonated molecules.
The data available in the literature indicate that both DESI
and SACI are highly promising techniques with the former giving
to mass spectrometry new application fields, and the latter
an increasing sensitivity and a lowering of chemical noise
that, in the case of biological samples, represent a weak
point in many analytical measurements.
[Back to top]
[Purchase
Article] [PMID:
19199883 PubMed - indexed for MEDLINE]
High-Energy Collision Induced Dissociation of Biomolecules:
MALDI-TOF/RTOF Mass Spectrometry in Comparison to Tandem Sector
Mass Spectrometry
Ernst Pittenauer and Günter
Allmaier
MALDI in combination with high-energy collision-induced
dissociation (CID) performed by tandem time-of-flight mass
spectrometry (TOF/RTOF) is a relatively new technology for
the structural analysis of various classes of biomolecules
as e.g., peptides, carbohydrates, glycoconjugate drugs and
lipids. Fragmentation mechanisms for these classes of compounds
as well as corresponding fragment ion nomenclatures based
mainly on data from tandem magnetic sector mass spectrometers
are summarized in this article. The major instrumental differences
between the present commercially available TOF/RTOFs are compiled
(e.g., ion gate, gas-collision cell, type of reflectron, etc.).
Whereas peptides have been investigated by MALDI-TOF/RTOF
and their CID spectra are well understood, other classes of
compounds (e.g., carbo-hydrates or lipids) are far less well
investigated. By comparing data from two different MALDI-TOF/RTOF-instruments,
it becomes evident that as they are operated at rather different
collision energies for CID (1 versus 20 keV) strong differences
in corresponding CID spectra for the same analyte are observed,
causing problems with library searches in data-bases as e.g.,
abundant peptide side-chain fragmentations mainly occurring
in the 8 to 20 keV collision regime are not considered. In
contrast, differences in CID spectra of carbohydrates among
different TOF/RTOF instruments are less clear-cut, because
the required collision energy is spread across a wide range.
Especially, carbohydrate cross-ring cleavages require less
collision energy in the keV-range than the corresponding peptide
side-chain fragmentations. Some of these carbohydrate cross-ring
fragmentations are even observed by very low energy CID (<
1 eV fragmentation amplitude). Similar observations can also
be made for glycoconjugates (e.g., the drug tylosin A). The
lipid class triacylglycerol needs rather high collision energies
for dissociating carbon-carbon bonds based upon classical
charge-remote fragmentation mechanisms. Comparison of high-energy
CID-data of ESI generated triacylglycerol precursors with
CID spectra from MALDI generated precursors shows different
mechanisms for charge-remote fragmentations. MALDI-TOF/RTOF-instruments
operated in the elevated high-energy CID mode exhibit a strong
potential in structural analysis of natural and synthetic
biomolecules with information often not obtainable by low
energy CID.
[Back to top]
[Purchase
Article] [PMID:
19199884 PubMed - indexed for MEDLINE]
MALDI Mass Spectrometry Imaging, from its Origins up to Today:
The State of the Art
Simona Francese, Francesca R. Dani, Pietro
Traldi, Guido Mastrobuoni, Giuseppe Pieraccini and
Gloriano Moneti
Mass Spectrometry (MS) has a number of features namely
sensitivity, high dynamic range, high resolution, and versatility
which make it a very powerful analytical tool for a wide spectrum
of applications spanning all the life science fields. Among
all the MS techniques, MALDI Imaging mass spectrometry (MALDI
MSI) is currently one of the most exciting both for its rapid
technological improvements, and for its great potential in
high impact bioscience fields. Here, MALDI MSI general principles
are described along with technical and instrumental details
as well as application examples. Imaging MS instruments and
imaging mass spectrometric techniques other than MALDI, are
presented along with examples of their use. As well as reporting
MSI successes in several bioscience fields, an attempt is
made to take stock of what has been achieved so far with this
technology and to discuss the analytical and technological
advances required for MSI to be applied as a routine technique
in clinical diagnostics, clinical monitoring and in drug discovery.
[Back to top]
[Purchase
Article] [PMID:
19199885 PubMed - indexed for MEDLINE]
The Effect of Post-Translational and Process-Induced Modifications
on the Multistage Gas-Phase Fragmentation Reactions of Protonated
Peptides
Jennifer M. Froelich and Gavin
E. Reid
Significant effort has been extended in recent years
toward the development and application of ‘targeted’
approaches for the identification, characterization and quantitative
analysis of post-translational or process-induced protein
modifications, based on the multistage tandem mass spectrometry
(MS/MS and MS3) fragmentation
reactions of their proteolytically derived peptide ions. Although
these approaches have been successfully employed to date,
the development of an improved understanding of the mechanisms
and other factors (e.g., proton mobility, peptide conformation,
product ion structures, etc.) that influence the multistage
fragmentation reactions of modified peptide ions would facilitate
further advances in the field. In this review, the important
role of such mechanistic studies for rationalizing the effect
of post-translational (e.g., phosphoserine- and phosphothreonine-containing
peptides) and process-induced (e.g., oxidative modifications
of methionine- and S-alkyl cysteine-containing peptides) protein
modifications on the multistage collision induced dissociation
gas-phase fragmentation reactions of proteolytically derived
peptide ions are highlighted. Furthermore, recent efforts
toward the development of chemical derivatization strategies
for controlling and directing the gas-phase fragmentation
reactions of protonated peptides toward the formation of analytically
useful fragmentation pathways will be discussed, as well as
the use of alternative dissociation techniques including electron
capture dissociation (ECD) and electron transfer dissociation
(ETD).
[Back to top]
[Purchase
Article] [PMID:
19199886 PubMed - indexed for MEDLINE]
Offline and Online Liquid Chromatography Mass Spectrometry
in Quantitative Proteomics
Jessica Z. Bereszczak and Francesco
L. Brancia
Hyphenation with liquid chromatography has become indispensable
in mass spectrometry-based proteomics. Sample complexity together
with the large variations in dynamic range can be only tackled
using techniques that isolate and/or concentrate individual
components prior to mass spectrometric analysis. In this review
the most recent developments in micro/nanoliquid chromatography
interfaced with MALDI and electrospray ionisation are discussed.
Particular attention is focused on all applications related
to quantitative proteomics.
[Back to top]
[Purchase
Article] [PMID:
19199887 PubMed - indexed for MEDLINE]
Recent Developments in Proteome Informatics for Mass Spectrometry
Analysis
James C. Wright and Simon J. Hubbard
Mass spectrometry has become the pre-eminent analytical
method for the study of proteins and proteomes in post-genome
science. The high volumes of complex spectra and data generated
from such experiments represent new challenges for the field
of bioinformatics. The past decade has seen an explosion of
informatics tools targeted towards the processing, analysis,
storage, and integration of mass spectrometry based proteomic
data. In this review, some of the more recent developments
in proteome informatics will be discussed. This includes new
tools for predicting the properties of proteins and peptides
which can be exploited in experimental proteomic design, and
tools for the identification of peptides and proteins from
their mass spectra. Similarly, informatics approaches are
required for the move towards quantitative proteomics which
are also briefly discussed. Finally, the growing number of
proteomic data repositories and emerging data standards developed
for the field are highlighted. These tools and technologies
point the way towards the next phase of experimental proteomics
and informatics challenges that the proteomics community will
face.
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[Purchase
Article] [PMID:
19199888 PubMed - indexed for MEDLINE]
Using Electrospray Ionisation Mass Spectrometry to Study Non-Covalent
Interactions
Bryan J. McCullough and Simon J.
Gaskell
The key strengths of electrospray over any other ionisation
techniques are its soft nature and its ability to produce
multiply charged ions. This combination is ideal for the study
of non-covalent interactions. In this review article, we cover
the basics of studying non-covalent interactions by mass spectrometry
- illustrated with examples from our own and other labs -
and discuss the current mass spectrometry based methods used
for understanding and characterising non-covalent protein
complexes.
[Back to top]
[Purchase
Article] [PMID:
19199889 PubMed - indexed for MEDLINE]
The Importance of Steroidomics in the Study of Neurodegenerative
Disease and Ageing
William J. Griffiths and Yuqin
Wang
In this mini review, the importance of experimental steroidomics
in the study of neurodegenerative disease and aging is discussed.
Attention is focused on just one class of lipid which is based
on the cyclopentanoperhydro-phenanthrene ring system. Experimental
methods for steroidomic analysis are reviewed, and the potential
to use these methods to diagnose disease and to gain a better
understanding of neurodegenerative disorders is examined.
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