Chemical Modification of Biological Polymers

Chemical

Modification

of Biological

Polymers

K12213

ISBN: 978-1-4398-4898-2

9 781439 848982

9 0 0 0 0

Examining the chemical modification of biological polymers and the

emerging applications of this technology, Chemical Modification of

Biological Polymers reflects the change in emphasis in this subsection

of biotechnology from the study of protein structure and function toward

applications in therapeutics and diagnostics.

Highlights

• The basic organic chemistry of the modification proteins, nucleic

acids, oligosaccharides, polysaccharides, and their applications

• New analytical technologies used to characterize the chemical

modification of biological polymers

• Identification of in vivo, non-enzymatic chemical modification

of biological polymers

• Specific chemical modifications to generate biopharmaceutical

products

This book covers the basics on the organic chemistry underlying the

chemical modification of biopolymers, including updates on the use of

various chemical reagents. It describes the current status of chemical

modification of biological polymers and emerging applications of this

technology in biotechnology. These technologies are important for the

manufacture of conjugate proteins used in drug delivery, for the prepara￾tion of nucleic acid microarrays, and for the preparation of hydrogels

and other materials used in tissue engineering.

Chemical Modification

of Biological Polymers

Biochemistry

of Biological Polymers

Chemical Modification







 

Approaches to the Conformational Analysis of Biopharmaceuticals

Roger L. Lundblad

Application of Solution Protein Chemistry to Biotechnology

Roger L. Lundblad

Approaches to the Conformational Analysis of Biopharmaceuticals

Roger L. Lundblad

Development and Application of Biomarkers

Roger L. Lundblad

Chemical Modification of Biological Polymers

Roger L. Lundblad

CRC Press is an imprint of the

Taylor & Francis Group, an informa business

Boca Raton London New York

Chemical

Modification

of Biological

Polymers

CRC Press

Taylor & Francis Group

6000 Broken Sound Parkway NW, Suite 300

Boca Raton, FL 33487-2742

© 2012 by Taylor & Francis Group, LLC

CRC Press is an imprint of Taylor & Francis Group, an Informa business

No claim to original U.S. Government works

Version Date: 20110720

International Standard Book Number-13: 978-1-4398-4900-2 (eBook - PDF)

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This book is dedicated to

Dr. Christine Vogel Sapan and other students who

have become colleagues over time and

provided continued inspiration through

insightful and penetrating questions.

vii

Contents

Preface.......................................................................................................................ix

Acknowledgments......................................................................................................xi

Author..................................................................................................................... xiii

Chapter 1 Functional Groups in Biopolymers and Factors Influencing

Reactivity..............................................................................................1

References........................................................................................... 14

Chapter 2 Modification of Amino/Amidino Groups in Proteins.........................25

α-Amino Groups (N-Terminal Amino Groups)...................................25

Modification of Arginine..................................................................... 74

References...........................................................................................84

Chapter 3 Modification of Hydroxyl and Carboxyl Functional Groups

in Proteins......................................................................................... 115

Serine and Threonine......................................................................... 115

Tyrosine............................................................................................. 116

Carboxyl Groups............................................................................... 140

References......................................................................................... 147

Chapter 4 Modification of Heterocyclic Amino Acids: Histidine

and Tryptophan................................................................................. 167

Histidine............................................................................................ 167

Tryptophan........................................................................................ 191

References......................................................................................... 201

Chapter 5 Modification of Sulfur-Containing Amino Acids in Proteins.......... 215

Cystine...............................................................................................277

Methionine........................................................................................297

References.........................................................................................303

viii Contents

Chapter 6 Chemical Modification of Nucleic Acids.......................................... 343

References.........................................................................................368

Chapter 7 Chemical Modification of Polysaccharides....................................... 383

References.........................................................................................397

ix

Preface

This work is intended to provide a comprehensive review of the chemical modifica￾tion of biopolymers including proteins, nucleic acids, and polysaccharides. That said,

I clearly understand that I have missed considerable information. This has become

painfully apparent as I used multiple information retrieval systems. An article that

might be found by one system istotally missed by othersystems. Thisis compounded

by my own personal retrieval system, which is based on some 45+ years of work￾ing in protein chemistry. So, apologies to those investigators whom I have missed;

I would appreciate receiving notice of omitted materials. The explosion in current

literature has compounded the problem as has what appears to be a total breakdown

in any effort to standardize abbreviations and acronyms.

I have tried to document the development and use of reagents rather than focusing

exclusively on current use. In doing this, I have taken the liberty of including some

personal observations about some studies, most notably those in the laboratories

of Stanford Moore and William Stein at the Rockefeller Institute (now Rockefeller

University).

Perusal of any contents of current biochemistry journal, even those with protein

or proteomics in the title, will show that the chemical modification of biopolymers is

not a “hot” topic. However, I still felt that the material in this book should be placed

into a format that can be more easily retrieved in today’s electronic environment.

That said, I am mightily suspicious of the current electronic environment (see The

Shallows by Nicholas Carr). Regardless of format, I hope that this information will

be of value to current investigators.

Roger L. Lundblad

Chapel Hill, North Carolina

xi

Acknowledgments

I am indebted to the usual suspects, including the long-suffering and patient Barbara

Norwitz and equally patient and even longer-suffering Jill Jurgensen for their help

in bringing this material to print. I am also indebted to Professor Bryce Plapp at the

University of Iowa for his continued and somewhat inexplicable patience with the

thermodynamically challenged.

xiii

Author

Roger L. Lundblad is a native of San Francisco, California. He received his under￾graduate education at Pacific Lutheran University and his PhD in biochemistry at the

University of Washington. After postdoctoral work in the laboratories of Stanford

Moore and William Stein at The Rockefeller University, he joined the faculty of the

University of North Carolina at Chapel Hill. He joined the Hyland Division of Baxter

Healthcare in 1990. Currently, Dr. Lundblad works as an independent consultant at

Chapel Hill, North Carolina, and writes on biotechnological issues. He is an adjunct

professor of pathology at the University of North Carolina at Chapel Hill.