Chemical Glycobiology - ACS Publications - American Chemical Society

Downloaded by 80.82.77.83 on May 18, 2018 | https://pubs.acs.org Publication Date: September 1, 2008 | doi: 10.1021/bk-2008-0990.pr001

Preface Chemical Glycobiology is an emerging sub-field of Chemical Biology, a multidisciplinary field that focuses on applying chemical techniques and tools to study and manipulate biology systems. Centered on understanding the biological roles of carbohydrates in nature, Chemical Glycobiology is diverse and involves disciplines ranging from chemical and enzymatic synthesis to assay development, through drug development and glycobiology. Carbohydrates are biomolecules that are abundant in nature. They play key roles in a broad range of physiologically and pathologically important processes, including cellular recognition and communication, signal transduction, immune responses, bacterial and viral infection, development, and tumor metastasis. With the rapid advancement of basic scientific research in glycochemistry and glycobiology, the importance of carbohydrates in the management and prevention of many diseases caused by human infectious agents has been repeatedly acknowledged. Many promising pharmaceutical applications of carbohydrate-based materials are currently emerging. A n increasing number of chemists and biochemists are developing interests in the Chemical Glycobiology field. Chemical glycobiologists need to fully master the concepts of both glycochemistry and glycobiology in order to answer biological questions efficiently, either by directly probing/targeting living systems at the molecular level with small molecules or by applying more traditional bioorganic/medicinal chemistry or pharmacology/biochemistry approaches by synthesizing compound libraries and developing efficient assay methods (e.g., highthroughput screening approaches) to identify lead compounds. In order

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to advance the Chemical Glycobiology field, it is essential for scientists from different disciplines to meet to exchange knowledge and share ideas and research findings. The 2-day Chemical Glycobiology Symposium in the 232 American Chemical Society (ACS) National Meeting in San Francisco, California provided a symposium platform to stimulate discussion and collaboration. The symposium established a stronger connection of Glycochemistry and Glycobiology. In order to share information with non-meeting participants and to attract more scientists to this rapidly advancing Chemical Glycobiology field, we assembled this A C S Symposium Series book. The book serves as an introduction to current advances in Chemical Glycobiology for students, scientists, and engineers, including those from industry, academia, and government, who are currently in the fields of chemical glycobiology, carbohydrate chemistry, glycobiology, natural product, and other carbohydrate-related research; it also introduces Chemical Glycobiology to those whose research will soon involve knowledge of this emerging field. This symposium series book describes the current progress of research in Chemical Glycobiology, including the development of chemical synthetic methods for carbohydrates, recent advances in chemoenzymatic synthesis of complex oligosaccharides and glycoconjugates, synthesis and application of glycolipids, cancer vaccine development and its clinical evaluation, as well as new tools developed for Chemical Glycobiology. The slow progress in the past towards the understanding of biolog ical roles of carbohydrates was mainly due to the difficulties in obtaining homogeneous compounds and the lack of efficient analyzing tools. The importance of synthetic method development has been increasingly noticed. Novel synthetic methods, including chemical, enzymatic, and chemoenzymatic methods have emerged. The first four chapters report the advanced chemical synthetic methods for producing monosaccha rides, oligosaccharides, glycosylated natural products, polysaccharides, peptidoglycans, and glycopeptide analogs. The first chapter by O'Doherty et al. provides a summary on de novo synthesis of mono saccharides, oligosaccharides, and glycosylated natural products. The second chapter by Huang et al. presents a comparison of conventional chemical approaches and the newly developed iterative one-pot strategy in producing hyaluronic acid oligosaccharides for biological studies. The


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third chapter by Mobashery and co-workers reports their practice and methods used by others in synthesizing the components of bacterial cell wall including peptidoglycans as well as lipid I, II and IV. In Chapter 4, Witczak reviews the synthetic studies of his laboratory in developing glycosyl thio-carboamino peptides as small glycopeptide derivatives to understand the function of specific glycopeptide moieties in glyco proteins. Two examples of recent advances in chemoenzymatic synthesis of complex oligosaccharides and glycoproteins are shown in Chapter 5 and Chapter 6. In Chapter 5, Chen and co-workers summarize their effort in using a highly efficient one-pot three-enzyme system in the synthesis of α2,3- and α2,6-linked sialoside libraries and their endeavor in develop ing a high-throughput screening platform to study substrate specificities of sialidases. L . - X . Wang describes in Chapter 6 the recent advances in the synthesis of large, homogeneous N-linked glycopeptides by endoglycosidase-catalyzed transglycosylation. Glycosphingolipids have been found to stimulate immune effector cells and have potential in treating cancer and other diseases. Chapter 7 by Gervay-Hague et al. summaries the current progess in synthesizing αlinked glycolipids and presents the advantage of applying glycosyl iodides in producing both O- and C-linked glycolipid analogs. P. G . Wang et al. reported in Chapter 8 their studies in the synthesis of α-Gal ceramide and isoglobotrihexosylceramide derivatives by varying the structures of lipid, modifying the terminal monosaccharide structures, and changing linkers to produce metabolically stable analogs. The difference of the obtained derivatives in stimulating immune effector cells is also reported. Oligosaccharides, polysaccharides, and glycoproteins have been found as tumor-associated antigens. There are on-going studies on developing glycovaccines. Holmberg et al. report in Chapter 9 a successful clinical study of cancer immunotherapy by treating breast and ovarian cancer patients using a carbohydrate-protein conjugate vaccine Theratope (Sialyl Tn-keyhole limpet hemocyanin). Chapter 10 by Linhardt and co-workers presents the synthesis and evaluation of Cglycoside derivatives of sialyl Tn and polysialic acid (PSA) as potential non-hydrolyzeable glycovaccines. The last four chapters report the currently developed tools and methods for Chemical Glycobiology. Lebrilla et al. in Chapter 11

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described an automated Mass Spectrometry-bated method for determining the site of glycosylation and the heterogeneic oligosaccharide structures in glycoproteins. Agard summarizes in Chapter 12 the unique metabolic engineering approach to study protein posttranslational modifications by introducing a chemical handle to the carbohydrate moieties in glycoconjugates of live cells and animals. In order to achieve the ultimate automated synthesis of carbohydrates, Pohl focuses on the development of fluorous tag-based strategy. The fluorous tag incorporated into the synthetic scheme also allows the direct transfer of the carbohydrate products to microarrays for high-throughput screening of carbohydrate-binding proteins. The strategy and application are discussed in Chapter 13. The interactions of carbohydrate and proteins are multivalent binding events. Development of polymers with multivalent carbohydrate units is curitical to truly understand these important events. The final chapter by Kiick and co-workers describes the design, synthesis, and evaluation of polypeptides of defined secondary structure and size as scaffolds to present galactose residues. It provies a novel platform for studying the multivalent interactions of carbohydrate and protein. Enjoy reading and join us to the exciting field of Chemical Glycobiology!

Acknowledgements We are pleased to acknowledge the financial support of the National Institute of Allergy and Infectious Diseases (NIH R13AJ073074), Wyeth Research, Genzyme Corporation, and the A C S Division of Carbohydrate Chemistry for the Chemical Glycobiology Symposium. We are greatful for the dedication and the support from the Office of Research and the Business Office of the Department of Chemistry at the University of California, Davis. The help from the administrative personnels of the A C S Division of Carbohydrate Chemistry in organizing the symposium is greatly appreciated. We would also like to sincerely thank our symposium speakers, meeting participants, and especially the authors and peer reviewers for their contributions. The

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publication of this book will not be possible without the dedication of personnels from the A C S Books Department.

Xi Chen Department of Chemistry University of California, Davis One Shields Avenue Davis, CA 95616


Randall Halcomb Gilead Sciences 333 Lakeside Dr. Foster City, CA 94404

Peng George Wang Departments of Biochemistry and Chemistry The Ohio State University 876 Biological Sciences Building 484 West 12th Avenue Columbus, O H 43210

xiii Chen et al.; Chemical Glycobiology ACS Symposium Series; American Chemical Society: Washington, DC, 2008.

Chemical Glycobiology - ACS Publications - American Chemical Society

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