Applications of synthetic carbohydrates to chemical biology

Lepenies, Bernd; Yin, Jian; Seeberger, Peter H.

doi:10.1016/j.cbpa.2010.02.016

Cited by 140 publications

(97 citation statements)

References 58 publications

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“…Studies of such important macromolecules were often hampered by the inherent diversity in composition as well as stereochemistry of glycosidic bonds. While recent approaches 3,4 have greatly improved our ability to control the stereooutcome of glycosylation reactions, an efficient and universal method is still highly sought after, especially one that is applicable for large-scale as well as combinatorial chemistry.…”

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confidence: 99%

The intriguing dual-directing effect of 2-cyanobenzyl ether for a highly stereospecific glycosylation reaction

Hoang

Liu

2014

Nat Commun

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The diverse presence as well as their very specific bio-responses of glycoconjugates found in all living species requires scientists to synthesize the precise structure of these complex oligosaccharides for various studies on glycoscience. Very few approaches were able to offer the sole a-or b-glycosylated products, even at the cost of complicating the preparative route or usage of exotic chiral auxiliaries to drive the stereoselectivity. In this report, the unification of solvent assistance and neighbouring group participation concepts have led us to the use of 2-cyanobenzyl ether as the dual-directing auxiliary for stereospecific construction of a-and b-glycosidic bonds from a single starting material, and both isomers can be obtained in exclusive stereoselectivity. This work demonstrates the difference in reactivities of glycosyl acceptors can be employed to completely drive the stereoselectivity, drawing the parallel comparison with the arming/disarming concept, which has been exclusively confined to glycosyl donors.

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confidence: 99%

The intriguing dual-directing effect of 2-cyanobenzyl ether for a highly stereospecific glycosylation reaction

Hoang

Liu

2014

Nat Commun

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“…For the automated synthesis of carbohydrates, phosphates, thiols, and trichloroacetimidates have been proven to be useful leaving groups (Plante et al 1999;Routenberg Love and Seeberger 2004;Seeberger 2008). (Seeberger 2008) For vaccines and carbohydrate-based diagnostics, automation of carbohydrate synthesis has large potential (Lepenies et al 2010;Seeberger and Werz 2005). Additional applications using choosing glycans as starting scaffolds may prove to be superior to any other biopolymer due to their intrinsic building block diversity.…”

Section: Automated Carbohydrate Synthesismentioning

confidence: 98%

High-Throughput Synthesis of Diverse Compound Collections for Lead Discovery and Optimization

Rademacher

Seeberger

2015

New Approaches to Drug Discovery

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Small-molecule intervention of protein function is one central dogma of drug discovery. The generation of small-molecule libraries fuels the discovery pipeline at many stages and thereby resembles a key aspect of this endeavor. High-throughput synthesis is a major source for compound libraries utilized in academia and industry, seeking new chemical modulators of pharmacological targets. Here, we discuss the crucial factors of library design strategies from the perspective of synthetic chemistry, giving a brief historic background and a summary of current approaches. Simple measures of success of a high-throughput synthesis such as quantity or diversity have long been discarded and replaced by more integrated measures. Case studies are presented and put into context to highlight the cross-connectivity of the various stages of the drug discovery process.

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“…A major interest in mucins is to analyze its various forms of O-glycopepitdes in relation to cancer-specific autoantibodies [22,23]. Chemical synthetic approaches have also been made to develop an O-glycopeptide library [24] as well as medical applications of the synthetic compounds designed from a chemical biological viewpoint [25]. In comparison with N-glycoproteins, however, it is much more difficult to treat with naturally occurring mucins, because they are generally protease resistant and are highly heterogeneous.…”

Section: Because They Are Difficultmentioning

confidence: 99%

Lectin‐based structural glycomics: A practical approach to complex glycans

2011

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Glycans exist in nature in various forms of glycoconjugates, i.e., glycoproteins, glycolipids, and glycosaminoglycans, either in soluble or membrane-bound forms. One of their prominent properties distinguished from nucleic acids and proteins is "heterogeneity" largely attributed to their inherent features of biosynthesis. In general, various methods based on the physicochemical principles have been taken for their separation and structural determination although all of them require prior liberation of glycans and appropriate labeling. On the other hand, a series of carbohydrate-binding proteins, or "lectins," have extensively been used in a more direct manner for cell typing, histochemical staining, and glycoprotein fractionation. Although most procedures conventionally used are useful, unfortunately they lack "throughput" comparable to a performance required for current omics studies. Recently, a novel technique called lectin microarray has attracted increasing attention from not only glycoscientists but also researchers in other fields, because it is straightforward and also informative. The method is innovating in that it enables direct approach to glycoconjugates such as glycoproteins and even cells without liberation of glycans from the core substrate, and therefore can be effectively applied for the sake of differential profiling in various fields. Concept, strategy, and technical advancement of lectin microarray are described. Also, as an introduction to glycomics, the authors explain the motivation to challenge this theme.

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Applications of synthetic carbohydrates to chemical biology

Cited by 140 publications

References 58 publications

The intriguing dual-directing effect of 2-cyanobenzyl ether for a highly stereospecific glycosylation reaction

The intriguing dual-directing effect of 2-cyanobenzyl ether for a highly stereospecific glycosylation reaction

High-Throughput Synthesis of Diverse Compound Collections for Lead Discovery and Optimization

Lectin‐based structural glycomics: A practical approach to complex glycans

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