Synthetic Glycomes

Wanyi Guan, Lei Li, Peng George Wang

• Publisher: Royal Society of Chemistry
• Year: 2019
• ISBN:
  9781788017770
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Biochemistry
• Index: Biological Sciences

Glycans play essential roles in diverse biological and etiological processes and their structural complexity endow various functions. The glycome is the entire set of glycans produced by an individual organism. As the glycan microarray emerged, a good amount of knowledge has been obtained in understanding the functions of glycans. However, limited accessibility of glycans is a major obstacle to the functional glycomics study. Although isolation from biology samples provided some structures, the low abundance of glycans obtained and the difficulty in complete structural assignment restricted the subsequent assay. To circumvent this limitation, many synthetic strategies, including chemical, enzymatic and chemo-enzymatic ones have been developed to make libraries of structurally defined complex glycans available. The glycans provided by these techniques combined with high-throughput glycoarray techniques have broadened and deepened our understanding about functional glycomics. The aim of this book is to provide a comprehensive review of the current state of the synthetic glycome and a brief introduction of the application of the synthetic glycome in glycoarray assay. Accordingly, synthetic strategies toward generating glycans with comprehensive structures as well as the glycoarrays to unveil the glycan functions are described in this book.

CHAPTER 1

Introduction: Glycome and the Glyco-toolbox

Shuaishuai Wang^a, Garrett A. Edmunds^a, Lei Li^a, Congcong Chen^a, ^b, ^c and Peng G. Wang^*a

^a Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA

^b National Glycoengineering Research Center, Shandong University, Jinan, Shandong 250012, China

^c School of Pharmaceutical Science, Shandong University, Jinan, Shandong 250012, China
^*E-mail:[email protected]

Carbohydrates, nucleic acids, and proteins comprise the three major macromolecules found in mammalian systems. As genomics and proteomics represent the studies of nucleic acids and proteins, respectively, the term “glycomics” describes the systematic study of the complete repertoire of glycans. Unlike genomics and proteomics, which both have methods for sequencing, automatic synthesis, and amplification, glycomics is comparatively underdeveloped. In this chapter, the challenge, opportunities, and achievement of glycomics and the development of the “glyco-toolbox” will be discussed.

1.1 Introduction

Biologists have broken down the different aspects in the study of life into various “-omics”. While the exact boundaries are increasingly ill-defined and nebulous, an “-omic” can generally be defined as the study of the structures, functions, and – most importantly – the roles of the biomolecules that make up the “-ome” of interest. Genomics is the study of the complete genome of a living thing, encompassing DNA, its structure, and how the information contained within the genetic code is encoded, modified, and passed on. Similarly, proteomics is the study of the entirety of an organism's proteome and their interactions.

Building off these definitions, glycomics is the study of the glycome – and its interactions – present in an organism. It is a study not just of individual components, but of the entirety of glycans and how they interact. Glycomics is an underdeveloped field compared with the sister fields of genomics and proteomics. This discrepancy is largely due to the time these fields have had to mature, the general interest by researchers and funding agencies, and the ease of manipulating the biomolecules of interest. More recently, as the roles of glycans have been more understood in biological systems, developing the field of glycomics has been increasingly prioritized by researchers. Key to this progress is the development of the synthetic glycome.

With the development of new technologies, the biological functions of carbohydrates were found to span the spectrum from development, growth, maintenance, and survival of the organism. For example, studies into clinical applicability arose early with the discovery of the human blood groups, with studies showing evidence that some blood antigens were glycans, such as ABO blood type and P1Pk type. The ABO blood group is determined by the glycan information on the surface of a red blood cell. Different modifications of the core glycan structure, the H antigen, are responsible for the different ABO blood groups. When the H antigen is present on a red blood cell's surface, anti-A and anti-B antibodies will be generated, meaning only type O can be accepted when transferring the blood (Table 1.1). On the other hand, a person that displays A and B antigens – blood type AB – without the anti-A and anti-B antibodies, can accept blood from the other three blood types. Of course, considerations should be made for other kinds of blood group systems, such as the Rh system.

Table 1.1ABO blood types and carbohydrate antigens. Symbols and abbreviations:

N-acetylgalactosamine (GalNAc),

galactose (Gal),

N-acetylglucosamine (GlcNAc),

fucose (Fuc)

Blood type	Type O	Type A	Type B	Type AB
Antigen	H antigen	A antigen	B antigen	A antigen and B antigen
Antibodies in plasma	Anti-A and Anti-B	Anti-B	Anti-A	None

As each “-omic” field matures and progresses, success and progress in research have largely depended on three ideas: access to the desired biomolecules, accurate means for analysis of those biomolecules, and the ability to manipulate and direct these structures for desirable applications. As more tools for various -omic toolboxes are developed for access, analysis, and application, foundational understandings give way to more complete and developed concepts and designs. In order to better understand these concepts, we must first understand the large diversity within the glycome and how it impacts synthetic efforts.

One of the major stumbling blocks in the development of glycomics is the sheer size of the theoretical glycome. This is in large part due to the diversity seen within the glycome...

Table of contents

• Cover
• Title
• Title
• Title
• Copyright
• Contents
• Contents
• Chapter 1 Introduction: Glycome and the Glyco-toolbox 1
• Chapter 2 Methodologies in Chemical Syntheses of Carbohydrates 15
• Chapter 3 Synthetically Useful Glycosyltransferases for the Access of Mammalian Glycomes 46
• Chapter 4 Chemical Synthesis of  N-Glycans 83
• Chapter 5 Chemoenzymatic Synthesis of N-Glycans 105
• Chapter 6 Chemoenzymatic Synthesis of α-Dystroglycan O-Mannose Glycans 125
• Chapter 7 Chemical Synthesis of Glycopeptides and Glycoproteins 151
• Chapter 8 Synthesis of Chondroitin Sulfate Oligosaccharides and Chondroitin Sulfate Glycopeptides 172
• Chapter 9 Chemoenzymatic Synthesis of Heparan Sulfate and Heparin 207
• Chapter 10 Synthesis of Glycosphingolipids (GSLs) 226
• Chapter 11 Enzymatic and Chemoenzymatic Synthesis of Human Milk Oligosaccharides (HMOS) 254
• Chapter 12 Synthesis of Marine Polysaccharides/Oligosaccharides and Their Derivatives 281
• Chapter 13 Glycan Production by Bacterial Fermentation 311
• Chapter 14 Solid-phase Glycan Synthesis 331
• Chapter 15 Reverse Synthesis of Natural Glycans 356
• Chapter 16 Novel Technologies for Quantitative O-Glycomics and Amplification/Preparation of Cellular O-Glycans 370
• Chapter 17 Current Stage of Commercially Available Glycans to Support Realization of Biologic Drugs 393
• Chapter 18 Glycan Microarrays with Semi-synthetic Neoglycoconjugate Probes in Understanding Glycobiology 421
• Chapter 19 Current Stage of Commercial Glycan Microarrays 447