General Aspects of the Glycosidic Bond Formation

Demchenko, Alexei V.

doi:10.1002/9783527621644.ch1

Cited by 63 publications

(34 citation statements)

References 199 publications

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“…Construction of the α-glycosidic linkage between the ribofuranose and the adenosine 2’-hydroxyl involves creation of a 1,2-cis-furanoside, a major challenge of synthetic carbohydrate chemistry18. Additionally, nucleosides are traditionally challenging substrates for chemical glycosylation due to the reactivity of the nitrogenous base19,20.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Dimeric ADP-Ribose and Its Structure with Human Poly(ADP-ribose) Glycohydrolase

et al. 2015

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Poly(ADP-ribosyl)ation is a common post-translational modification that mediates a wide variety of cellular processes including DNA damage repair, chromatin regulation, transcription, and apoptosis. The difficulty associated with accessing poly(ADP-ribose) (PAR) in a homogeneous form has been an impediment to understanding the interactions of PAR with poly(ADP-ribose) glycohydrolase (PARG) and other binding proteins. Here we describe the chemical synthesis of the ADP-ribose dimer, and we use this compound to obtain the first human PARG substrate-enzyme co-crystal structure. Chemical synthesis of PAR is an attractive alternative to traditional enzymatic synthesis and fractionation, allowing access to products such as dimeric ADP-ribose, which has been detected but never isolated from natural sources. Additionally, we describe the synthesis of an alkynylated dimer and demonstrate that this compound can be used to synthesize PAR probes including biotin and fluorophore-labeled compounds. The fluorescently labeled ADP-ribose dimer was then utilized in a general fluorescence polarization-based PAR-protein binding assay. Finally, we use intermediates of our synthesis to access various PAR fragments and evaluation of these compounds as substrates for PARG reveals the minimal features for substrate recognition and enzymatic cleavage. Homogeneous PAR oligomers and unnatural variants produced from chemical synthesis will allow for further detailed structural and biochemical studies on the interaction of PAR with its many protein binding partners.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Dimeric ADP-Ribose and Its Structure with Human Poly(ADP-ribose) Glycohydrolase

et al. 2015

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“…3-8 In the past three decades, much effort has been dedicated to refining glycosylation reaction conditions. 9 However, enhancements resulting from this effort are still not sufficient to control the outcome of many glycosylations. Thioglycosides serve as a prime example of this, even though they have been one of the most studied and applied classes of glycosyl donors.…”

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confidence: 99%

Direct Synthesis of Diastereomerically Pure Glycosyl Sulfonium Salts

2011

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“…Selenoglycosides can also be used as tools for the investigation of sugar‐protein interactions . From a synthetic point of view, they show a unique reactivity as glycosyl donors: indeed, the C‐Se bond can be readily ionized under photo‐chemical and electro‐chemical conditions, generating very reactive cationic and radical‐cationic species. However, the preparation of selenoglycosides involves major limitations: generally, only one anomer is accessible, the synthesis is not trivial and the substrate scope narrow (for instance, unprotected sugars are not tolerated under the reaction conditions).…”

Section: Exocyclic Oxygen Replacementmentioning

confidence: 99%

Design and synthesis of glycomimetics: Recent advances

Tamburrini

Colombo

Bernardi

2019

Medicinal Research Reviews

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In the past few decades, our understanding of glycan information‐encoding power has notably increased, thus leading to a significant growth also in the design and synthesis of glycomimetic probes. Combining data from multiple analytical sources, such as crystallography, nuclear magnetic resonance spectroscopy, and other biophysical methods (eg, surface plasmon resonance and carbohydrate microarrays) has allowed to shed light on the key interaction events between carbohydrates and their protein‐targets. However, the low metabolic stability of carbohydrates and their high hydrophilicity, which translates in low bioavailability, undermine their development as drugs. In this framework, the design of chemically modified analogues (called carbohydrate mimics or glycomimetics) appears as a valid alternative for the development of therapeutic agents. Glycomimetics, as structural and functional mimics of carbohydrates, can replace the native ligands in the interaction with target proteins, but are designed to show enhanced enzymatic stability and bioavailability and, possibly, an improved affinity and selectivity toward the target. In the present account, we specifically focus on the most recent advances in the design and synthesis of glycomimetics. In particular, we highlight the efforts of the scientific community in the development of straightforward synthetic procedures for the preparation of sugar mimics and in their preliminary biological evaluation.

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General Aspects of the Glycosidic Bond Formation

Cited by 63 publications

References 199 publications

Synthesis of Dimeric ADP-Ribose and Its Structure with Human Poly(ADP-ribose) Glycohydrolase

Synthesis of Dimeric ADP-Ribose and Its Structure with Human Poly(ADP-ribose) Glycohydrolase

Direct Synthesis of Diastereomerically Pure Glycosyl Sulfonium Salts

Design and synthesis of glycomimetics: Recent advances

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