Editorial Cite This: Chem. Rev. 2018, 118, 7865−7866
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Introduction: Carbohydrate Chemistry he last thematic issue on carbohydrates in Chemical Reviews was in late 2000, just as I was setting up my lab as an assistant professor. I immediately bought a copy in those pre-electronic-journal days for my nascent group; it is still in my lab but now well worn. Interestingly, that issue begins with an editorial by James Bashkin titled “CarbohydratesA Hostile Scientific Frontier Becomes Friendlier.”1 Fortunately, in the intervening 18 years, this scientific frontier has not only become friendlier but gained many allies in the process. They are needed. The frontier has only grown with increasing knowledge of the roles of carbohydrates in everything from how an antibody spurs an immune response to how carbohydrates develop the infant microbiome. Chemistry is now often the bottleneck to the development of a sophisticated understanding and use of this class of biomoleculesas was true for nucleic acids and proteins before the invention of tools and techniques such as the polymerase chain reaction and automated solid-phase synthesis. A United States National Academy of Sciences (NAS) report in 20122 nicely outlined the issues in its call for scientists to focus their effortsa call now heard by the US NIH Common Fund among othersto improve the tools available for the glycosciences in an incredibly ambitious 10-year timeline. This issue serves as a sort of interim report for those worldwide efforts as well as a cry for new explorers. The NAS report begins with a call to develop the tools that would make synthetic glycans readily available. Central to many efforts in the study of carbohydrates is this ability to make structurally well-defined glycans in sufficient quantity and purity for study. Kulkarni et al. introduce the topic of chemical synthesis in contrast to enzymatic synthesis with the basics of building block protection, deprotection, and glycosylation and then survey current “one-pot” approaches to these synthetic challenges. They end with a brief summary of automated synthesis methods, a topic taken up in more depth at the end of this section on chemical synthesis. Nielsen and Pedersen then chart efforts to develop catalytic glycosylation methods with some attention to mechanistic concerns. Adero et al. outline the experimental evidence for what we now know about glycosylation mechanisms and thereby also introduce current methods used to identify carbohydrate structures. Bennett and Galen elaborate the trials in finding good ways of making glycosides with the 2-position deoxygenateda motif found in a variety of glycosylated natural products. To complete the hike through the chemical synthesis of glycans, Panza et al. discuss in more detail the challenges and successes in automating the synthesis of chemical oligosaccharide in order to broaden the impact of chemical synthesis as a means to obtain pure glycans. Obtaining pure authentic standards through chemical synthesis is becoming increasingly feasible. However, challenges remain in detecting, identifying, and purifying glycans from natural sources. Herein, Lu et al. summarize the state-ofthe-art in the separation of glycans using capillary electrophoresis and Ruhaak et al. describe the use of mass
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spectrometry to analyze glycomes and glycoproteins. Mass spectrometry coupled to other techniques and to informatics tools is becoming increasingly powerful for the analysis of glycans. Molecular modeling and nuclear magnetic resonance are also a fundamental part of glycan analysis today. Woods discusses the current capabilities of NMR spectroscopy and carbohydrate modeling along with the principles of predicting oligosaccharide conformations, the modeling of carbohydrate− protein complexes, and related docking experiments. The NAS report also calls for an enlarged toolbox of enzymes and enzyme inhibitors to aid in the study of glycans. The increasing availability of glycosyltransferases and related enzymes is now enabling efforts toward automating oligosaccharide synthesis using enzymes as discussed by Wen et al. Enzymes are also proving valuable in combination with chemical methods to synthesize glycolipids and glycoproteins. Hunter et al. discuss advances in chemical as well as joint chemical and enzymatic strategies to making vertebrate glycosylated sphingolipid structures, including analogs of these structures for use as chemical probes. Chao and Wang then map current methods to use enzymes to make glycopeptides and glycoproteins. Finally, the NAS report also identifies education as a key hurdle to growing the glycosciences and their impact. Basic undergraduate chemistry textbooks might contain a sidebar on some modern aspect of carbohydrate chemistry but largely focus on very old chemistry; most instructors somehow never manage to get to that chapter tucked into the back of the book somewhere. This thematic issue is itself designed to help researchers and the teachers of graduate students and advanced undergraduates. However, ideally this knowledge would perfuse the curriculum far earlier. To that end, Pirinelli and Koviach-Côté have assembled and analyzed what is currently available for adoption in schools everywhere. This outlook also makes apparent by their absence the pedagogical holes that require much additional creative effort to fill in the coming years. Although Bashkin’s quoted collective sigh of “Difficult chemistry, difficult biology, difficult analysis” is still warranted, this issue should make clear that new ideas and new talent are starting to make the impossible quite reasonable. Many basic mammalian glycans can now be identified, purified, modeled, and synthesized, and with this understanding more bridges to biology and materials science3,4 are being constructed. Since 2000, though, the size of the frontier has expanded greatly, especially with the discovery of the crucial role that microbiomes play in the health and function of plants and animals and the role that diverse carbohydrates play in those microbiome interactions. New allies are still welcome and necessary to help explore and enjoy this huge terrain!
Nicola L. B. Pohl*
Special Issue: Carbohydrate Chemistry Published: September 12, 2018 7865
DOI: 10.1021/acs.chemrev.8b00512 Chem. Rev. 2018, 118, 7865−7866
Chemical Reviews
Editorial
Indiana University Bloomington
AUTHOR INFORMATION Corresponding Author
*E-mail:
[email protected]. ORCID
Nicola L. B. Pohl: 0000-0001-7747-8983 Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS. Biography Nicola L. B. Pohl (Nikki) was born in Montreal, Canada, and was raised in Georgia and South Carolina in the United States. She majored in English and American literature and languages with the comparative study of religions as an undergraduate at Harvard College. She also took chemistry classes and did gas-phase ion research with Prof. Joesph Grabowski while in Cambridge. She then helped start the laboratories of Prof. Laura Kiessling as a graduate student at the University of WisconsinMadison, where she earned her Ph.D. in organic chemistry in 1997. After a U.S. National Institutes of Health postdoctoral fellowship in the Department of Chemical Engineering at Stanford University doing metabolic engineering with Prof. Chaitan Khosla, she started her independent career at Iowa State University. In 2012, she moved to Indiana University. She is currently a professor of chemistry and holds the Joan and Marvin Carmack Chair in Bioorganic Chemistry and from 2017−2018 was a fellow of the Radcliffe Institute at Harvard University and a visiting professor at the Massachusetts Institute of Technology. She serves on the editorial advisory boards of Organic Letters and The Journal of Organic Chemistry. Her research interests focus on developing synthetic, analytical, and automated methods including the design of digital native reactionsto help understand and thereby exploit the differential reactivity and shapes of carbohydrates.
ACKNOWLEDGMENTS N.P. wishes to thank the Joan and Marvin Carmack Fund at Indiana University and the Radcliffe Institute for Advanced Study for the Edward, Frances, and Shirley B. Daniels Fellow position to help her put together this thematic issue and for recent support for her laboratory’s work on carbohydrates from the U.S. National Science Foundation under CHE-1362213 and the U.S. National Institutes of Health Common Fund Glycosciences Program [1U01 GM116248]. REFERENCES (1) Bashkin, J. CarbohydratesA Hostile Scientific Frontier Becomes Friendlier. Chem. Rev. 2000, 100, 4265. (2) National Research Council (US) Committee. (2012) Transforming Glycoscience: A Roadmap for the Future, National Research Council (US) Committee on Assessing the Importance and Impact of Glycomics and Glycosciences. National Academies Press (US), Washington, D.C. (3) See for example the recent thematic issue on supramolecular chemistry: Miura, Y.; Hoshino, Y.; Seto, H. Glycopolymer Nanobiotechnology. Chem. Rev. 2016, 116, 1673−1692. (4) See for example the recent thematic issue on supramolecular chemistry: Delbianco, M.; Bharate, P.; Varela-Aramburu, S.; Seeberger, P. H. Carbohydrates in Supramolecular Chemistry. Chem. Rev. 2016, 116, 1693−1752.
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DOI: 10.1021/acs.chemrev.8b00512 Chem. Rev. 2018, 118, 7865−7866
