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More About This Title Co- and Post-Translational Modifications of Therapeutic Antibodies and Proteins
English
A Comprehensive Guide to Crucial Attributes of Therapeutic Proteins in Biological Pharmaceuticals
With this book, Dr. Raju offers a valuable resource for professionals involved in research and development of biopharmaceutical and biosimilar drugs. This is a highly relevant work, as medical practitioners have increasingly turned to biopharmaceutical medicines in their search for safe and reliable treatments for complex diseases, while pharmaceutical researchers seek to expand the availability of biopharmaceuticals and create more affordable biosimilar alternatives.
Readers receive a thorough overview of the major co-translational modifications (CTMs) and post-translational modifications (PTMs) of therapeutic proteins relevant to the development of biotherapeutics. The majority of chapters detail individual CTMs and PTMs that may affect the physicochemical, biochemical, biological, pharmacokinetic, immunological, toxicological etc. properties of proteins. In addition, readers are guided on the methodology necessary to analyze and characterize these modifications. Thus, readers gain not only an understanding of CTMs/PTMs, but also the ability to design and assess their own structure-function studies for experimental molecules. Specific features and topics include:
- Discussion of the research behind and expansion of biopharmaceuticals
- Twenty chapters detailing relevant CTMs and PTMs of proteins, such as glycosylation, oxidation, phosphorylation, methylation, proteolysis, etc.
- Each chapter offers an introduction and guide to the mechanisms and biological significance of an individual CTM or PTM, including practical guidance for experiment design and analysis
- An appendix of biologic pharmaceuticals currently on the market, along with an assessment of their PTMs and overall safety and efficacy
This volume will prove a key reference on the shelves of industry and academic researchers involved in the study and development of biochemistry, molecular biology, biopharmaceuticals and proteins in medicine, particularly as biopharmaceuticals and biosimilars become ever more prominent tools in the field of healthcare.
English
T. Shantha Raju has more than 20 years of experience in the research and development of biotherapeutics, including monoclonal antibodies and glycoproteins. Dr. Raju has published over 40 research articles, several reviews and book chapters and serves on the editorial boards of several leading journals.
English
Preface
About the author
Abbreviations used in this book
Chapter 1 Introduction to Co- and Post-Translational Modifications of Proteins
Chapter 2 Acetylation of Proteins
Introduction
Mechanism of N-acetylation at the N-termini of proteins
Mechanism of N-acetylation and N-deacetylation of lysine residues
Mechanism of O-acetylation of sugar residues
Biological Significance of Protein Acetylation
Acetylation in Recombinant Therapeutic Proteins
Methods to analyze acetylation in proteins and carbohydrates
Chapter 3 C-Terminal Lys or Arg Clipping in Proteins
Introduction
Biological Significance of C-Terminal Lys or Arg Clipping in Proteins
Analysis of C-terminal Lys or Arg Clipping in Proteins
Chapter 4 Cysteinylation of Proteins
Introduction
Biological Significance of Cysteinylation of Proteins
Cysteinylation and Trisulfide Bonds in Recombinant Therapeutic Proteins
Analysis of Cysteinylation of proteins
Chapter 5 Deamidation of Proteins
Introduction
Mechanism of Deamidation of Proteins
Physicochemical Characteristics of Deamidated Proteins
Biological Significance of Deamidation of Proteins
Deamidation and Immunogenicity
Deamidation and Pharmacokinetics Properties of Proteins
Deamidation in Recombinant Therapeutic Proteins
Methods for the analysis of Deamidation in Proteins
Chapter 6 Glycation of Proteins
Introduction
Mechanism of Protein Glycation
Glycation of Proteins in human
Protein Glycation and human diseases
Glycation in Recombinant Therapeutic Proteins
Methods to Analyze Protein Glycation
Chapter 7 Glycosylation of Proteins
Introduction
Glycans and Aglycans
Glycosidic Bonds
Aldoses and Ketoses
Anomeric Groups: α- and β-Configurations
Natural Diversity of Glycans
Glycans and Enzymes
N-Glycosylation
O-Glycosylation
Phospho-Serine Glycosylation
GPI-Anchors (Glypiation)
C-Mannosylation
Chapter 8 N-Glycosylation of Proteins
Introduction
Mechanism of N-Glycosylation of Proteins
Microheterogeneity of N-Glycans
Species Specific N-Glycosylation
Functions of N-Glycans
N-Glycosylation in Recombinant Therapeutic Proteins
Methods to analyze N-glycans
Chapter 9 O-Glycosylation of Proteins
Introduction
Biosynthesis of O-Glycans
Physicochemical Properties of O-Glycosylated Proteins
Biological Functions of O-Glycans
O-Glycosylation in Recombinant Therapeutic Proteins
Analysis of O-Glycans
Chapter 10 Hydroxylation of Proteins
Introduction
Mechanism of Hydroxylation
Lysyl 5-Hydroxylase
Biological Significance of Hydroxylation
Hydroxylation in Recombinant Therapeutic Proteins
Analysis of Hydroxylation
Chapter 11 Methylation of Proteins
Introduction
Mechanism of Protein Methylation
Physicochemical and Biological Significance of Methylation of Proteins
Methylation in Recombinant Therapeutic Proteins
Methods to analyze methylation in proteins and glycoproteins
Chapter 12 Oxidation of Proteins
Introduction
Mechanism of Protein Oxidation
Oxidation in Recombinant Therapeutic Proteins
Analytical Methods to Measure Protein Oxidation
Chapter 13 Phosphorylation of Proteins
Introduction
Mechanism of protein phosphorylation in the living cells
Protein Kinases
Physicochemical and Biological functions of protein phosphorylation
Phosphorylation in Recombinant Therapeutic Proteins
Methods to analyze protein phosphorylation
Chapter 14 Prenylation of Proteins
Introduction
Mechanism of Protein Prenylation
Biological Significance of Prenylation of Proteins
Analysis of Prenylation of Proteins
Chapter 15 Proteolysis of Proteins
Introduction
Chemical Proteolysis
Enzymatic proteolysis
Biological Significance of proteolysis
Role of Proteolysis in human diseases
Use of proteases in laboratories
Sources of Proteases
Proteolysis in Recombinant Therapeutic Proteins
Analytical methods for the detection of proteolysis of proteins
Chapter 16 Selenylation
Introduction
Biological Significance of Selenylation of Proteins
Chapter 17 Signal Peptides
Introduction
Biological Significance of Signal Peptides
Signal Peptides in Recombinant Therapeutic Proteins
Chapter 18 Sulfation of Proteins and Glycoproteins
Introduction
Biosynthesis of PAPS
Sulfation reactions in the Cytosol
Sulfation in the Golgi compartments
Sulfation of Tyrosine Residues
Mechanism of Tyrosine Sulfation
Biological Functions of Tyr Sulfation
Sulfation of Glycosaminoglycans (GAGs) and Proteoglycans
Biological functions of GAGs
Sulfation in Recombinant Therapeutic Proteins
Analysis of sulfation in Biomolecules
Analysis of Tyr Sulfation
Analysis of Sulfated Glycoconjugates
Chapter 19 Sumoylation
Introduction
Mechanism of Sumoylation
Biological Significance of Sumoylation
Chapter 20 Ubiquitination
Introduction
Mechanism of Ubiquitination
Biological Significance of Ubiquitination
Chapter 21 Other CTMs and PTMs of Proteins
Adenylylation or AMPylation
ADP-Ribosylation
Amidation
Arginylation
Bytyrylation
Carbamylation
Carbonylation
Cittrullination
Diphthamide
Formylation
Gamma-Carboxylation
Glypiation
Hypusine formation
Iodination
Lipoylation
Malonylation
Myristoylation
Neddylation
Palmitoylation
Polyglutamylation
Polyglycylation
Propionylation
Pupylation
Pyroglutamate formation
S-Glutathionylation
S-Nitrosylation
