Kinetic and NMR spectroscopic study of the chemical stability and reaction pathways of sugar nucleotides

Jaakkola, Juho; Nieminen, Anu; Kivelä, Henri; Korhonen, Heidi; Tähtinen, Petri; Mikkola, Satu

doi:10.1080/15257770.2020.1856870

Cited by 3 publications

(7 citation statements)

References 32 publications

(77 reference statements)

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“…In the absence of enzymes, nucleotide sugars undergo a substitution at the anomeric carbon only under acidic conditions, where the oxocarbenium ion formed upon departure of the diphosphate moiety is stable enough to exist as an intermediate [143]. Under neutral and alkaline conditions, nucleotide sugars react by an intramolecular substitution at the phosphate, and two monophosphates are formed as products [143][144][145][146][147][148]. The acid and base-catalyzed reactions of UDP-Glc are shown in Scheme 6A.…”

Section: Chemical Reactions Of Nucleotide Sugarsmentioning

confidence: 99%

“…The difference in the reactivity is probably one of the reasons why nucleotide sugars are usually not used as glycosyl donors in the chemical synthesis of oligosaccharides. Under neutral and alkaline conditions, a neighboring HO group of the sugar attacks the phosphate, and a nucleoside monophosphate and a 1,2-cyclic sugar phosphate are formed (Scheme 6A) [143][144][145][146][147][148]. A cis orientation of the nucleophile and the phosphate is required for an efficient reaction; GDP-mannose with the adjacent OH in the trans position reacts more slowly, releasing GDP as the sole UV-active product [146] (Scheme 6B).…”

Section: Chemical Reactions Of Nucleotide Sugarsmentioning

confidence: 99%

“…A cis orientation of the nucleophile and the phosphate is required for an efficient reaction; GDP-mannose with the adjacent OH in the trans position reacts more slowly, releasing GDP as the sole UV-active product [146] (Scheme 6B). A nucleophilic attack of the adjacent 2-OH on C1 Under neutral and alkaline conditions, a neighboring HO group of the sugar attacks the phosphate, and a nucleoside monophosphate and a 1,2-cyclic sugar phosphate are formed (Scheme 6A) [143][144][145][146][147][148]. A cis orientation of the nucleophile and the phosphate is required for an efficient reaction; GDP-mannose with the adjacent OH in the trans position reacts more slowly, releasing GDP as the sole UV-active product [146] (Scheme 6B).…”

Section: Chemical Reactions Of Nucleotide Sugarsmentioning

confidence: 99%

“…Acids enhance the reaction by protonating the phosphate group, and bases increase the nucleophilicity of the attacking OH group by deprotonation [145]. A second-order rate constant of (1.6 ± 0.2)•10 −2 dm 3 mol −1 s −1 at 25 • C has been determined for the base-catalyzed cleavage of UDP-Gal [148]. The temperature dependence of the alkaline cleavage is fairly modest.…”

Section: Chemical Reactions Of Nucleotide Sugarsmentioning

confidence: 99%

“…The temperature dependence of the alkaline cleavage is fairly modest. Rate constants for the cleavage of UDP-Glc in 5 mM NaOH at different temperatures give an activation energy E a value of 61.8 kJmol −1 [149] and allow a rough estimation of two-fold rate increase for every ten degrees [148].…”

Section: Chemical Reactions Of Nucleotide Sugarsmentioning

confidence: 99%

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Nucleotide Sugars in Chemistry and Biology

Mikkola

2020

Molecules

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Nucleotide sugars have essential roles in every living creature. They are the building blocks of the biosynthesis of carbohydrates and their conjugates. They are involved in processes that are targets for drug development, and their analogs are potential inhibitors of these processes. Drug development requires efficient methods for the synthesis of oligosaccharides and nucleotide sugar building blocks as well as of modified structures as potential inhibitors. It requires also understanding the details of biological and chemical processes as well as the reactivity and reactions under different conditions. This article addresses all these issues by giving a broad overview on nucleotide sugars in biological and chemical reactions. As the background for the topic, glycosylation reactions in mammalian and bacterial cells are briefly discussed. In the following sections, structures and biosynthetic routes for nucleotide sugars, as well as the mechanisms of action of nucleotide sugar-utilizing enzymes, are discussed. Chemical topics include the reactivity and chemical synthesis methods. Finally, the enzymatic in vitro synthesis of nucleotide sugars and the utilization of enzyme cascades in the synthesis of nucleotide sugars and oligosaccharides are briefly discussed.

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Section: Chemical Reactions Of Nucleotide Sugarsmentioning

confidence: 99%

Section: Chemical Reactions Of Nucleotide Sugarsmentioning

confidence: 99%

Section: Chemical Reactions Of Nucleotide Sugarsmentioning

confidence: 99%

Section: Chemical Reactions Of Nucleotide Sugarsmentioning

confidence: 99%

Section: Chemical Reactions Of Nucleotide Sugarsmentioning

confidence: 99%

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Nucleotide Sugars in Chemistry and Biology

Mikkola

2020

Molecules

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5′-Chalcogen-Substituted Nucleoside Pyrophosphate and Phosphate Monoester Analogues: Preparation and Hydrolysis Studies

Mikkola

Eguaogie

Nieminen

et al. 2022

IJMS

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Novel sulfur and selenium substituted 5′,5′-linked dinucleoside pyrophate analogues were prepared in a vibration ball mill from the corresponding persilylated monophosphate. The chemical hydrolysis of pyrophosphorochalcogenolate-linked dimers was studied over a wide pH-range. The effect of the chalcogeno-substitution on the reactivity of dinucleoside pyrophosphates was surprisingly modest, and the chemical stability is promising considering the potential therapeutic or diagnostic applications. The chemical stability of the precursor phosphorochalcogenolate monoesters was also investigated. Hydrolytic desilylation of these materials was effected in aqueous buffer at pH 3, 7 or 11 and resulted in phosphorus-chalcogen bond scission which was monitored using 31P NMR. The rate of dephosphorylation was dependent upon both the nature of the chalcogen and the pH. The integrity of the P-S bond in the corresponding phosphorothiolate was maintained at high pH but rapidly degraded at pH 3. In contrast, P-Se bond cleavage of the phosphoroselenolate monoester was rapid and the rate increased with alkalinity. The results obtained in kinetic experiments provide insight on the reactivity of the novel pyrophosphates studied as well as of other types of thiosubstituted biological phosphates. At the same time, these results also provide evidence for possible formation of unexpectedly reactive intermediates as the chalcogen-substituted analogues are metabolised.

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Dynamic NMR methodology for kinetic studies

Wei

2024

ACE

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NMR (Nuclear magnetic resonance) is a popular tool used to characterize the structure of molecules, which is widely used for its high precision and accurate results. Due to these advantages, the NMR technique has been developed for monitoring the changes in the components during a reaction. This is called dynamic NMR technology. The kinetic measuring of a reaction is an important application of dynamic NMR, and the unique design of the methodology allows the NMR technique to be used for the determination of kinetic data such as reaction rates. In addition, dynamic NMR has also been used to monitor the reaction process and determine the reaction mechanism. Dynamic NMR techniques have developed rapidly in recent decades and have led to new research ideas and tools in chemistry and other related fields. In this paper, some examples of kinetic properties of reactions studied by dynamic NMR methods are introduced, including a summary of their development and prospects.

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Kinetic and NMR spectroscopic study of the chemical stability and reaction pathways of sugar nucleotides

Cited by 3 publications

References 32 publications

Nucleotide Sugars in Chemistry and Biology

Nucleotide Sugars in Chemistry and Biology

5′-Chalcogen-Substituted Nucleoside Pyrophosphate and Phosphate Monoester Analogues: Preparation and Hydrolysis Studies

Dynamic NMR methodology for kinetic studies

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