Mass Spectrometry–Based Glycoproteomics and Its Clinic Application

Mass Spectrometry–Based Glycoproteomics and Its Clinic Application PDF Author: Haojie Lu
Publisher: CRC Press
ISBN: 1000406601
Category : Science
Languages : en
Pages : 258

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Book Description
As one of the most extensive and important protein post-translational modifications, glycosylation plays a vital role in regulating organisms and is associated with various physiological and pathological processes. Recently, researchers have focused on the need to characterize protein glycosylation sites, structures, and their degree of modification, to better understand their biological functions while also looking for potential biomarkers for diagnosis and treatment of disease. Mass spectrometry (MS) is one of the most powerful tools used to study biomolecules including glycoproteins and glycans. With the continuous development of glycoproteomics and glycomics based on MS analysis, more techniques have evolved and contribute to understanding the structure and function of glycoproteins and glycans. This book reviews advancements achieved in MS-based glycoproteomic analysis, including a wide range of analytical methodologies and strategies involved in selective enrichment; as well as qualitative, quantitative, and data analysis, together with their clinical applications. Significant examples are discussed to illustrate the principles, laboratory protocols, and advice for key implementation to ensure successful results. Mass Spectrometry–Based Glycoproteomics and Its Clinic Application will serve as a valuable resource to elucidate new techniques and their applications for students, postdocs, and researchers working in proteomics, glycoscience, analytical chemistry, biochemistry, and clinical medicine. Editor: Haojie Lu is a professor at Fudan University, specializing in proteomics based on mass spectrometry with particular emphasis on novel technologies for separation and identification of low-abundant proteins and post-translationally modified proteins (including glycosylation), as well as relative and absolute quantification methods for proteomics.

Mass Spectrometry–Based Glycoproteomics and Its Clinic Application

Mass Spectrometry–Based Glycoproteomics and Its Clinic Application PDF Author: Haojie Lu
Publisher: CRC Press
ISBN: 1000406601
Category : Science
Languages : en
Pages : 258

Get Book Here

Book Description
As one of the most extensive and important protein post-translational modifications, glycosylation plays a vital role in regulating organisms and is associated with various physiological and pathological processes. Recently, researchers have focused on the need to characterize protein glycosylation sites, structures, and their degree of modification, to better understand their biological functions while also looking for potential biomarkers for diagnosis and treatment of disease. Mass spectrometry (MS) is one of the most powerful tools used to study biomolecules including glycoproteins and glycans. With the continuous development of glycoproteomics and glycomics based on MS analysis, more techniques have evolved and contribute to understanding the structure and function of glycoproteins and glycans. This book reviews advancements achieved in MS-based glycoproteomic analysis, including a wide range of analytical methodologies and strategies involved in selective enrichment; as well as qualitative, quantitative, and data analysis, together with their clinical applications. Significant examples are discussed to illustrate the principles, laboratory protocols, and advice for key implementation to ensure successful results. Mass Spectrometry–Based Glycoproteomics and Its Clinic Application will serve as a valuable resource to elucidate new techniques and their applications for students, postdocs, and researchers working in proteomics, glycoscience, analytical chemistry, biochemistry, and clinical medicine. Editor: Haojie Lu is a professor at Fudan University, specializing in proteomics based on mass spectrometry with particular emphasis on novel technologies for separation and identification of low-abundant proteins and post-translationally modified proteins (including glycosylation), as well as relative and absolute quantification methods for proteomics.

Mass Spectrometry-Based Glycoproteomics and Its Clinic Application

Mass Spectrometry-Based Glycoproteomics and Its Clinic Application PDF Author: Haojie Lu
Publisher: CRC Press
ISBN: 9781003185833
Category : Science
Languages : en
Pages : 280

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Book Description
As one of the most extensive and important protein post-translational modifications, glycosylation plays very important roles in the organism and is associated with different physiological and pathological processes. Therefore, there has been increasing attention and need to characterize protein glycosylation sites, structures and their modification degree, in order to understand well their biological functions or look for potential biomarkers for disease diagnosis and treatment.Mass spectrometry (MS) is one of the most powerful tools to study biomolecules including glycoproteins and glycans. With the continuous development of glycoproteomics and glycomics based on MS analysis, more and more techniques have appeared and contribute to understanding the structure and function of glycoproteins and glycans. Therefore, this book demonstrates the progress that has been achieved in MS-based glycoproteomic analysis, including a wide range of analytical methodologies and strategies involved in selective enrichment, qualitative analysis, quantitative analysis and data analysis, together with their clinical applications. And some significant examples will be discussed to illustrate the principles, laboratory protocols and key implementation advice to ensure successful results.This book will serve as a valuable resource to appropriate techniques and their applications for students, postdocs, and researchers working in proteomics, glycoscience, analytical chemistry, biochemistry, and clinical medicine, and so on.

Mass Spectrometry Based Protein Profiling

Mass Spectrometry Based Protein Profiling PDF Author:
Publisher:
ISBN: 9789461698162
Category :
Languages : en
Pages : 168

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Book Description


Mass Spectrometry-Based Chemical Proteomics

Mass Spectrometry-Based Chemical Proteomics PDF Author: W. Andy Tao
Publisher: John Wiley & Sons
ISBN: 1118970217
Category : Science
Languages : en
Pages : 448

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Book Description
PROVIDES STRATEGIES AND CONCEPTS FOR UNDERSTANDING CHEMICAL PROTEOMICS, AND ANALYZING PROTEIN FUNCTIONS, MODIFICATIONS, AND INTERACTIONS—EMPHASIZING MASS SPECTROMETRY THROUGHOUT Covering mass spectrometry for chemical proteomics, this book helps readers understand analytical strategies behind protein functions, their modifications and interactions, and applications in drug discovery. It provides a basic overview and presents concepts in chemical proteomics through three angles: Strategies, Technical Advances, and Applications. Chapters cover those many technical advances and applications in drug discovery, from target identification to validation and potential treatments. The first section of Mass Spectrometry-Based Chemical Proteomics starts by reviewing basic methods and recent advances in mass spectrometry for proteomics, including shotgun proteomics, quantitative proteomics, and data analyses. The next section covers a variety of techniques and strategies coupling chemical probes to MS-based proteomics to provide functional insights into the proteome. In the last section, it focuses on using chemical strategies to study protein post-translational modifications and high-order structures. Summarizes chemical proteomics, up-to-date concepts, analysis, and target validation Covers fundamentals and strategies, including the profiling of enzyme activities and protein-drug interactions Explains technical advances in the field and describes on shotgun proteomics, quantitative proteomics, and corresponding methods of software and database usage for proteomics Includes a wide variety of applications in drug discovery, from kinase inhibitors and intracellular drug targets to the chemoproteomics analysis of natural products Addresses an important tool in small molecule drug discovery, appealing to both academia and the pharmaceutical industry Mass Spectrometry-Based Chemical Proteomics is an excellent source of information for readers in both academia and industry in a variety of fields, including pharmaceutical sciences, drug discovery, molecular biology, bioinformatics, and analytical sciences.

Separation Techniques in Analytical Chemistry

Separation Techniques in Analytical Chemistry PDF Author: Rudolf Bock
Publisher: Walter de Gruyter GmbH & Co KG
ISBN: 3111182061
Category : Science
Languages : en
Pages : 642

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Book Description
The separation of a mixture into its individual components is one of the most fundamental procedures in analytical and industrial chemistry. This classic book in analytical chemistry provides a comprehensive yet systematic outline of all known separation methods. Through its detailed treatment of the basic principles of separation possibilities, it not only covers what is currently known, but also represents a treasure trove of methods that are still awaiting further development. It is clearly structured and contains interesting examples, further reading and a detailed index. An indispensable book for advanced students of natural sciences (chemistry, biochemistry, food chemistry, pharmacy, clinical chemistry, environmental sciences) and technology (chemical engineering, chemical-physical measurement & biotechnology), as well as teachers of these disciplines.

Chemical Glycoproteomics for Identification and Discovery of Glycoprotein Alterations in Human Cancer

Chemical Glycoproteomics for Identification and Discovery of Glycoprotein Alterations in Human Cancer PDF Author: David Spiciarich
Publisher:
ISBN:
Category :
Languages : en
Pages : 169

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Book Description
Changes in glycosylation have long been appreciated to be part of the cancer phenotype; sialylated glycans are found at elevated levels on many types of cancer and have been implicated in disease progression. However, the specific glycoproteins that contribute to cell surface sialylation are not well characterized, specifically in bona fide human cancer. Metabolic and bioorthogonal labeling methods have previously enabled enrichment and identification of sialoglycoproteins from cultured cells and model organisms. The goal of this work was to develop technologies that can be used for detecting changes in glycoproteins in clinical models of human cancer. In Chapter 1 of this dissertation, I present an overview of the structures and functions of glycans and their relationship to cancer progression. I also discuss applications of in vivo bioorthogonal labeling in model organisms and how in humans, the significant regulatory and ethical barriers associated with introducing chemically altered sugars into people have hindered it. Finally, I review mass spectrometry-based proteomics and how it can be applied to clinical glycoproteomics. In Chapter 2, I demonstrate the first application of this bioorthogonal labeling in a glycoproteomics platform applied to human tissues cultured ex vivo. Both normal and cancerous prostate tissues were sliced and cultured in the presence of functionalized derivatives of N-acetyl mannosamine, the sialic acid biosynthetic precursor. Chemical biotinylation followed by enrichment and mass spectrometry led to the identification of glycoproteins that were found at elevated levels or uniquely in cancerous prostate tissue. This work therefore extends the use of bioorthogonal labeling strategies to problems of human clinical relevance. Secretome proteins play important roles in regulation of many physiological processes and show utility as potential biomarkers and for noninvasive diagnostics and treatment monitoring. In Chapter 3, I discuss a platform for identifying sialoglycoproteins that were secreted in the conditioned media from bioorthogonally labeled human prostate tissue slice cultures. This platform could be used to identify disease biomarkers in a faithful clinical model of human disease. Mutations in granulocyte colony-stimulating factor 3 receptor (CSF3R), also known as G-CSFR, occur in the majority of patients with chronic neutrophilic leukemia (CNL) and are more rarely present in other kinds of leukemia. In Chapter 4, I discuss novel variants in CSF3R at asparagine residue N610, one of which was germline. Interestingly, these N610 substitutions are potently oncogenic and result in ligand-independent receptor activation. They confer activation of the JAK-STAT signaling pathway and concurrent sensitivity to JAK kinase inhibitors. The N610 residue is part of a consensus N-linked glycosylation motif in the receptor. Detailed mass spectrometry analysis demonstrates that this site is occupied by both complex and complex bisecting glycans. Further analysis demonstrates that N610 is the primary site of sialylation of the receptor. This study demonstrates that membrane-proximal N-linked glycosylation is critical for maintaining the ligand dependence of the receptor. Furthermore, it expands the repertoire of potently oncogenic mutations in CSF3R that are therapeutically targetable.

Advances in Glycoproteomics and Glyco-biomarker Discovery Studies

Advances in Glycoproteomics and Glyco-biomarker Discovery Studies PDF Author: Francisca Owusu Gbormittah
Publisher:
ISBN:
Category : Biochemical markers
Languages : en
Pages : 176

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Book Description
The development of analytical technologies to investigate the glycoproteome of clinical relevant samples has improved over the last 10 years. These new developments aim to improve the identification and quantification of disease-specific glyco-biomarkers, which are present at low amounts in biological matrices. Glyco-biomakers have the potential to significantly contribute to cancer discovery studies in specific areas such as; early diagnosis, prognosis, monitor cancer recurrence and improve the low survival rate of cancer. In this thesis, we focused on the development and application of novel liquid affinity chromatography fractionation platforms integrated with nano-LC-MS/MS to characterize and quantify the glycoproteome as well as selected glyco-biomarker candidates of cancer samples. In chapter 1, brief background information covering glycoproteomics and glyco-biomarker discovery studies is presented. Specifically, protein glycosylation process and how the field of 'omics', which includes glycoproteomics, have revolutionized clinical glyco-biomarkers discovery are discussed. Further, various disease models, current sample fractionation strategies and analytical methodologies involved in glyco-biomarker development pipeline and their significance as well as their short falls are described. Reviewing biomarker validation and current bio-infomatics tools utilized in glycoproteomics discovery studies concludes chapter 1. Chapter 2 details the development of a novel multi-dimensional affinity liquid chromatography fractionation approach that combines the depletion of the top 12 abundant proteins and multi-lectin fractionation of the human plasma. Evaluating and validating the reproducibility, specificity and overall recoveries of the platform demonstrated the suitability of the developed method in glyco-biomarker discovery studies of clinical samples. After establishing this robust platform, it was applied in chapter 3 to comprehensively study the global glycoproteome profile of clear cell renal cell carcinoma plasma (ccRCC) samples to identify and characterize potential biomarkers for early detection of the disease. During this study, protein abundance alterations as well as glycan shifts were investigated to understand the sub-proteome of ccRCC. Chapter 4 focuses on the structural characterization of a glycoprotein (clusterin) that was identified during the ccRCC biomarker discovery studies. Clusterin has been implicated in ccRCC cancer progression however; its structure and biological function(s) are not yet well defined. Therefore, to have more structural insights into clusterin, the protein was immuno-affinity purified from ccRCC plasma followed by tandem mass spectrometry to profile glycoforms, "N"-glycosylation sites and quantify glycan amounts. We discovered that the levels of bi-antennary digalactosylated disialylated (A2G2S2) and core fucosylated bi-antennary digalactosylated disialylated (FA2G2S2) glycans differed significantly in the plasma of patients before and after curative nephrectomy of localized ccRCC. In chapter 5, a multi-lectin affinity chromatography platform previously developed in our laboratory was optimized and applied to investigate glycoproteins and non-glycoproteins present in pancreatic cyst fluid samples. This study was aimed at identifying potential candidate markers for early detection of malignant cyst (pancreatic cancer precursor). Our data showed the identification of proteins with significant differential expression in mucinous cysts (malignant cyst) compared to non-mucinous cysts (benign) of which one protein (periostin) associated with cancer progression was confirmed by immunoblotting assay. In the final chapter (chapter 6), we summarize and conclude our findings in this work and provide our perspective on the potential of glycoproteins in glyco-biomarker discovery studies.

Mass Spectrometry-based Proteomics: from Deep Proteomes to Clinical Application

Mass Spectrometry-based Proteomics: from Deep Proteomes to Clinical Application PDF Author: Johannes Bruno Müller-Reif
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

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Book Description


Statistical Analysis of Proteomics, Metabolomics, and Lipidomics Data Using Mass Spectrometry

Statistical Analysis of Proteomics, Metabolomics, and Lipidomics Data Using Mass Spectrometry PDF Author: Susmita Datta
Publisher: Springer
ISBN: 3319458094
Category : Medical
Languages : en
Pages : 294

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Book Description
This book presents an overview of computational and statistical design and analysis of mass spectrometry-based proteomics, metabolomics, and lipidomics data. This contributed volume provides an introduction to the special aspects of statistical design and analysis with mass spectrometry data for the new omic sciences. The text discusses common aspects of design and analysis between and across all (or most) forms of mass spectrometry, while also providing special examples of application with the most common forms of mass spectrometry. Also covered are applications of computational mass spectrometry not only in clinical study but also in the interpretation of omics data in plant biology studies. Omics research fields are expected to revolutionize biomolecular research by the ability to simultaneously profile many compounds within either patient blood, urine, tissue, or other biological samples. Mass spectrometry is one of the key analytical techniques used in these new omic sciences. Liquid chromatography mass spectrometry, time-of-flight data, and Fourier transform mass spectrometry are but a selection of the measurement platforms available to the modern analyst. Thus in practical proteomics or metabolomics, researchers will not only be confronted with new high dimensional data types—as opposed to the familiar data structures in more classical genomics—but also with great variation between distinct types of mass spectral measurements derived from different platforms, which may complicate analyses, comparison, and interpretation of results.

Mass Spectrometry-Based Approaches for Treating Human Diseases and Diagnostics

Mass Spectrometry-Based Approaches for Treating Human Diseases and Diagnostics PDF Author: Thiago Verano-Braga
Publisher: Springer Nature
ISBN: 3031506243
Category :
Languages : en
Pages : 273

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Book Description