Table Of ContentSelected Topics in Mass Spectrometry
in the Biomolecular Sciences
NATO ASI Series
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Series C: Mathematical and Physical Sciences - Vol. 504
Selected Topics in
Mass Spectrometry in
the Biomolecular Sciences
edited by
Richard M. Caprioli
University of Texas,
Medical SChool,
Houston, Texas, U.SA
Antonio Malorni
SESMA-C.N.R.,
Napoli, Italy
and
Giovanni Sindona
Universita delia Calabria,
Dipartimento di Chimica,
Arcavacata di Rende, Italy
Springer·Science+Business Media, B.v.
Proceeclings of the NATO Advancecl Study Institute on
Mass Spectrometry in the Biomolecular Sciences
Altavilla-Milicia (PA), ltaly
7-18 July 1996
A C.I.P. Catalogue record for this book is available from the Library of Congress.
ISBN 978-94-010-6171-1 ISBN 978-94-011-5165-8 (eBook)
DOI 10.1007/978-94-011-5165-8
Printed on acid-free paper
AII Rights Reserved
© 1997 Springer Science+Business Media Oordrecht
Originally published by Kluwer Academic Publishers in 1997
Softcover reprint of the hardcover 1s t edition 1997
No part of the material protected by this copyright notice may be reproducecl or
utilizecl in any form or by any means, electronic or mechanical, including photo
copying, recording or by any information storage and retrieval system, without written
permission from the copyright owner.
CONTENTS
Preface. ..................................................................................................................................... IX
Contributing Authors ......................................................................................................... XI
Participants ........................................................................................................................ XVII
Part I: Methods in Mass Spectrometry
Electrospray Ionization: Theory and Application ............................................................................... 3
S. I. Gaskell. M. S. Bolgar.l. Riba and S. G. Summerfield
Atmospheric Pressure Ionization (ESI and APCI) Theory and Application ...................................... 17
A. Raffaelli
Matrix-Assisted Laser Desorpition-Ionization (MALDI) Mass Spectrometry: Principles and
Applications .................................................................................................................................... 33
M. Karas and U. Bahr
High Sensitivity ESI/MS and MALDI MS ....................................................................................... 55
T. B. Farmer and R. M. Caprioli
Optimised Ge/MS Interfacing Systems and Operating Conditions ................................................. 85
P. I. Arpino
Quantitative Analysis by Mass Spectrometry: Some Important Considerations .............................. I 03
M. W.Duncan
Optimization of Mass Spectrometric Ionisation Efficiency Data. .................................................... 121
I. T. Ozgen. O. Altungoz. B. Salih and B. G. M. Vandeginste
Role of Intemal Energy in Mass Spectrometric Fragmentation ...................................................... 129
K. Vekey
Interaction of Metal Ions and Protons with Simple Biomolecules.
Structure Information from Bond Energies and Entropy Effects .................................................... 143
B. A. Cerda. M. I. Nold. and C. Wesdemiotis
A Promising Marriage Between Theory and Experiment: Density Functional
Method Versus Mass Spectrometry ................................................................................................ 163
T. Marino. N. Russo. E. Sicilia and M. Toscano
vi
Part U : Instrumentation for Mass Analysis and Detection
Recent Advances in Magnet Sector Mass Spectrometry •............................................................... 183
O. V. Nemjrovslciy. J. K. Gooden. R. Ramanathan and M. L. Gross
Quadrupole Mass Filters and Quadrupole Ion Traps ..................................................................... 213
R. G. Cooks. G. Chen and C. Weil
Time-of-Flight Mass Spectrometry ............................................................................................... 239
ML. Vestal
Combined Analyzer Technologies ................................................................................................ 263
P. Kofel and U. P. Schlunegger
Fourier Transform Mass Spectrometry ............•............................................................................. 287
M. L. Easterling and I. J. Amster
Part m: Application to Biomolecules
Protein Characterization by MS in Pharmaceutical Industry.
Structural Characterization of Modified Forms of Recombinant
Hirudin Sequence Variant 1 and Direct Batch Analysis ................................................................ 3 17
D. Maller. P. Schindler. M. Coulot. W. J. Richter. W. Maerki and H. Grossenbacher
Folding Pathways of Disulphide Containing Proteins .................................................................... 347
M. Ruoppolo. F. Talamo. P. Pucci and G. Marino
Integration of Chemical Modification Reactions and Mass Spectrometric
Methods in Protein Characterisation .............................................................................................. 361
S. Foti
PSD-MALDI Analysis of Pep tides ................................................................................................. 377
B. Spengler
Development of a Mass Spectrometric Approach for the
Characterisation of Hemoglobin Adducts .............................................................................•......... 399
P. Ferranti. N. Sannolo. G. Mamone. G. Forte and A. Malorni
Reactivity of Antineoplastic Drugs with Model Peptides Studied by
Advanced Mass Spectrometry Methodologies ......................................................................•......... 413
V. Carbone. G. Pocs/alvi. N. Sannolo and A. Malorni
Applications of Mass Spectrometry in Biochemical Studies of Nucleosides,
Nucleotides and Nucleic Acids ........•...................................................................................•......... 42i
R. P.Newton
MALDI Mass Analysis of Oligonucleotides .................................................................................... 45:
U. Bahr and M. Karas
vii
DNA Adducts in Human Carcinogenesis. Clues to Etiology and Mechanism ................................. .465
H.Bartsch
MALDI MS of Oligo and Polysaccharides .................................................................................... .4 77
D. Garozzo
Mass Spectrometry of Isoeicosanoids as Novel Lipid Substances .................................................... 50 I
R. C. Murphy and R. J. Waugh
The Role of Mass Spectrometry in the Characterization of Plant Metabolites
from Crude Extracts ...................................................................................................................... 517
A. De Nino. A. Napoli and G. Sindona
Environmental Applications of Mass Spectrometry: Toxaphene Analysis ...................................... 533
Fl. Onuska and RJ. Maguire
The Detennination of Polar Compounds in the Aquatic Environment ............................................ 559
M. J. F. Suter
Some Mass Spectrometry Contributions in the Study of Cultural Heritage ..................................... 575
P. Agozzino
Index .......................................................................................................................................... 581
PREFACE
1llis book is the result of efforts of both young and senior scientists who met together in Altavilla
Milicia (Italy) on July 1996 on the occasion of the NATO advanced study institute (ASI) in Mass
Spectrometry in Biomolecular Sciences. The recent developments in instrumentation and
methodologies of mass spectrometry have been discussed in this beautiful area of the
Mediterranean located on the island of Sicily.
The aim of the book is to provide young scientists with accounts of the recent developments of
methods and applications in biomolecular sciences. It was decided therefore to present in part I
only those ionization methods such as electrospray and MALDI techniques which are currently
under development and refmement Two chapters have been devoted to GC/MS and quantitative
analysis and four contributions deal with the physical-chemical aspects of the methodology.
In part II are presented the recent achievements in instrumentation for mass analysis and detection
which are especially suited for the detection and characterization of biological molecules.
In part III of the book applications of methods and instrumentation to biomolecules are presented.
An extensive coverage of the impact of mass spectrometric methods in protein analysis on
pharmaceutical industry is given. Three more contributions explore the possibility of obtaining
structural information from intact proteins with reference to their secondary structure as well. The
protein/peptide subject also includes two chapters related to the contribution of the methodology to
cancer therapy. A unique tool in DNA studies is provided by mass spectrometry which can be used
in the analysis of a variety of compounds. from small nucleosides up to large oligonucleotides. In
addition it also plays a role in the evaluation of DNA adducts in human carcinogenesis. the object
of three of the chapters in part III. The importance of conventional and desorption ionization
methods in the characterization of polysaccharides. lipids and plant metabolites is also examined,
together with the role that mass spectrometry plays in the control of the environment and in the
preservation of worlc of arts from pollution.
The editors acknowledge the special effort of the lecturers who have contributed to this book.
Special thanks go to the NATO scientific affairs division. the Italian National Research Council
(Rome). The University of Palermo. the University of Calabria and the manufacturers Micromass
(UK). Thermo (US) • Perkin-Elrner-Sciex (US). Broker (GER) Perseptives (US) who provided
most of the funds for the institute. The editors also thank the French Society for Mass
Spectrometry (SFSM). the Portuguese JNeT. Turkish TUBITAK. Greek Ministry of Industry.
Energy and Technology and the U.S. National Science Foundation for providing travel grants to
some junior participants at the ASI.
R. M. Caprioli
A. Malorni
G. Sindona
June. 1997
IX
CONTRIBUTING AUTHORS
P. Agozzino Dipartimento di Olimica e Tecnologie Fannaceutiche, UniversitA eli
PaleJUlo, Via Archirafi 32, 90123 PaleJUlo, Italy
O. Altungoz Department of Chemistry, Imlir Institute of Tecimology, Gaziosmanpasa
Bulvari 16, Cankaya Imlir, Turkey
J. Amster Department of Otemistry, University of Georgia. Athens Georgia 30602-
2556, Usa
P. Arpino Laboratoire de (]limie Analytique, Institut National Agronomique, 16
rue Qaude Bernard, 75231 Paris-05, France
U. Bahr Institute for Physical and Theoretial Otemistry, Department of
Instrumental Analytical Otemistry, University of Frankfurt, Theodor
Stern-Kai 7, 60590 Frankfurt, GeJUlany
H. Bartsch GeJUlan Cancer Research Center, 1m Neuenheimer Feld 280, 0-69120
Heidelberg, Getmany
M. S. Bolgar Michael Barber Centre for Mass Spectrometry, Department of
Otemistry, UMIST, Manchester M60 lQO, UK
R. M. Caprioli Analytical Otemistry Center, Department of Biochemistry and
Molecular Biology, University of Texas Medical School, P.O. Box
20708, Houston, Tx 77225
V. Carbone Servizio di Spettrometria di Massa del CNR c/o FacoltA di Medicina
dell'UniversitA di Napoli Federico n, Via Pansini 5, I - 80131 Napoli,
Italy
B. A. Cerda Department of Otemistry, University of Akron, Akron, OH 44325-3601,
Usa
G.Oten Department of Otemistry, Purdue University, West Lafayette IN 47907,
Usa
R. G. Cooks Department of Otemistry, Purdue University, West Lafayette IN 47907,
Usa
M. Coulot Central Research Services, Ciba-Geigy Ltd, Ot-4002 Basel, Switzerland
A. De Nino Oipartimento di Otimica. UniversitA della Calabria, 1-87030 Arcavacata
di Rende (CS), Italy
xi
XII
M. W.Duncan Biomedical Mass Spectrometry, Unit University of New South Wales,
Sydney, Australia
M. L. Easterling Department of Cllemistry, University of Georgia, Athens Georgia 30602-
2556, Usa
T. B. Fanner Analytical Otemistry Center, Department of Biochemistry and
Molecular Biology, University of Texas Medical School, P.O. Box
20708, Houston, Tx 77225
P. Ferranti Servizio di Spettrometria di Massa del CNR c/o FacoltA di Medicina
dell'UniversitA di Napoli Federico II, Via Pansini 5, I - 80131 Napoli,
Italy
G. Forte Servizio di Spettrometria di Massa del CNR c/o FacoltA di Medicina
dell'UniversitA di Napoli Federico II, Via Pansini 5, I - 80131 Napoli,
Italy
S.Foti Dipartimento di Scienze Otimiche, UniversitA di Catania, Viale A. Doria
6,95125 Catania, Italy
D. Garozzo Istituto per la Chimica e la Tecnologia dei Materiali Polimerici, Viale A
Doria 6, 95125 Catania, Italy
S. J. Gaskell Michael Barber Centre for Mass Spectrometry, Department of
Otemistry, UMIST, Manchester MOO lQD, UK
J. K. Gooden Department of Chemistry, Washington University, One Brookings Drive,
St Louis, Missouri 63130, Usa
M.L. Gross Department of Chemistry, Washington University, One Brookings Drive,
St. Louis, Missouri 63130, Usa
H. Grossenbacher Core Drug Discovery Technologies, Ciba-Geigy Ltd, CH4002 Basel,
Switzerland
M. Karas Institute for Physical and Theoretial Otemistry, Department of
Instrumental Analytical Chemistry, University of Frankfurt, Theodor
Stern-Kai 7, 60590 Frankfurt, Gennany
P.Kofel Institute of Organic Otemistry, University of Bern Freiestr. 3, CH-30l2
Bern, Switzerland
A. Napoli Dipartimento di Otimica, UniversitA della Calabria, 1-87030 Arcavacata
di Rende (CS), Italy
