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Biopolymer Mass Spectrometry. Methods, Ion Chemistry, Bioanalytical Applications

  • ID: 3695816
  • Book
  • 400 Pages
  • John Wiley and Sons Ltd
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The development of innovative, efficient ionization techniques allowing a gentle desorption of even complex molecules has provided mass spectrometry with the breakthrough in the direct analysis of biopolymers. Applicable in various disciplines and yet more powerful than almost any other method, the spectrum of compounds investigated ranges from macromolecular chemistry via biochemistry right up to molecular biology. In this way, suitable mass spectroscopic techniques determine not only the primary structure of proteins but also provide an insight into their spatial structure, even allowing structural and functional analyses. The simplicity of electrospray MS for analyzing non–covalent biomacromolecular complexes opens up brand new perspectives for supramolecular chemistry as well as molecular recognition processes. The combination of efficient separation techniques such as affinity chromatography or new methods directly monitoring biomolecular interactions (biosensors) with mass spectrometry provides the basis for diagnotic platforms in clinical applications.

In his book, the internationally renowned expert Michael Przybylski provides a comprehensive overview of this still relatively young methodology, which will soon be as much an integral part of biopolymer structure analysis as X–ray crystallography and NMR spectroscopy.
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INTRODUCTION: FUNDAMENTALS OF BIOPOLYMER MASS SPECTROMETRY

History and instrumental development of biopolymer mass spectrometry

Analytical preconditions for mass spectrometry of macromolecules

Scope of interdisciplinary application areas

IONIZATION METHODS FOR BIOPOLYMER MASS SPECTROMETRY

Desorption– Ionisation Methods for Biopolymer Ion Formation –

Initial developments

Field Desorption

252–Cf Plasma Desorption & Fast Atom Bombardment

Matrix–Assisted Laser Desorption– Ionisation (MALDI)

Electrospray– Ionisation (ESI)

New Developments of Ionisation Techniques

INSTRUMENTATION FOR BIOPOLYMER MASS SPECTROMETRY

Analysers for Macromolecular Mass Spectrometry

Magnetic Sector Analysers

Quadrupole Mass Analysers

Time–of–Flight Mass Analysers

Ion Trap Mass Analysers

Hybrid Analysers

High Resolution Mass Spectrometers for Biopolymers

Fouriertransform– ICR Mass Spectrometry

Orbitrap Mass Spectrometry

Ion Detection and Spectra Acquisition

Preconditions for Macromolecular Ion Detectors

Spectra acquisition & data evaluation methods

Special High Mass Ion Detectors

SEPARATION TECHNIQUES AND HYBRID SYSTEMS FOR BIOPOLYMER MASS SPECTROMETRY

Liquid Chromatography– Mass Spectrometry

Size Exclusion Chromatography

Combination with Gel and Capillary Electrophoresis

Bioaffinity– Mass Spectrometry

Ion Mobility Mass Spectrometry

Online Biosensor– MS

METHODS FOR STRUCTURE DETERMINATION OF BIOPOLYMERS

Molecular Weight Determination

Mechanisms of Biopolymer Ion Formation

Mass Resolution and Accuracy of Macromolecular Ions

Methods for Primary Structure Determination of Polypeptides

Fragmentation of Polypeptide Ions for Tandem–MS Sequence Determination

Chemical and Enzymatic Degradation for Sequence Determination

Approaches for "Top–Down" Sequence Determination

Structural Characterization of Polypeptides by Chemical Modification Combined with Mass Spectrometry

Chemical Modification Reactions for Structure Analysis

Structural Characterisation using Crosslinking Reactions

Analysis of Non–covalent Supramolecular Biopolymer Complexes

Preconditions for Analysis of Non–covalent Interactions

Specificity Analysis of Biopolymer Complexes

Correlation of Solution and Gas Phase Structures of Biopolymer Complexes

Characterisation of Higher Order Biopolymer Structures

"Charge Structures" of ESI– MS of Biopolymers

Ion Mobility– Mass Spectrometry of Polypeptides

HD– Exchange Approaches for Probing Biopolymer Interactions

Chemical Labelling Approaches for Probing Protein Interaction Structures

Characterisation of Biopolymer– Ligand Interactions by Proteolytic Degradation Combined with Mass Spectrometry

Fast Photochemical Oxidation of Proteins (FPOP) and Mass Spectrometry

BIOCHEMICAL APPLICATIONS OF BIOPOLYMER MASS SPECTROMETRY

Introduction

Sample Preparation and Handling in Bioanalytical Applications

Liquid–Liquid Extraction (LLE)

Solid Phase Extraction (SPE)

Solid Phase Microextraction and Supercritical Fluid Extraction (SFE)

Immunoaffinity Extraction (IAE) & Affinity–Isolation

Applications to Primary Structure Analysis of Biopolymers

Protein Sequence Determination

Sequencing and Mutation Analysis in Polynucleotides

Structure Determination of Carbohydrates

Mass Spectrometric Proteome Analysis

Analysis of Post–Translational Protein Structure Modifications

Phosphorylation

Glycosylation

Fatty Acid Acylation

Oxidative Modification of Proteins

Ubiquitin Conjugation

Selected Applications to Analysis of Biopolymer Interactions

Carbohydrate Interactions of Lectins

Structure Analysis of Ion Channels by Chemical Modification and Mass Spectrometry

BIOMEDICAL APPLICATIONS OF BIOPOLYMER MASS SPECTROMETRY

Analysis of Recognition Structures in Molecular Immunology

Identification of Polypeptide Antigen Epitopes

Identification of Antibody Paratopes

Characterization of Oligomerization– Aggregation Pathways in Target Proteins of Neurodegenerative Diseases

Applications to Clinical Diagnostics of Lysosomal Storage Diseases Enzymes

Clinical Applications of Affinity– Mass Spectrometry to Autoimmune Diseases

PERSPECTIVES OF BIOPOLYMER MASS SPECTROMETRY
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Michael Przybylski
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