The Synthesis and Conformation of Dihydroxypiperidinyl Derivates of Nucleobases as Novel Iminosugar Nucleoside Analogs

Rejman, Dominik; Pohl, Radek; Dračínský, Martin

doi:10.1002/ejoc.201001610

Cited by 9 publications

(9 citation statements)

References 31 publications

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“…The rotation around this bond is sterically hindered by neighboring substituents. Similar hindered rotation was also observed for a dihydroxypiperidinyl derivative of uracil when the substituent was attached to nitrogen N3 …”

Section: Recent Examples Of the Determination Of Na Adduct Structuresupporting

confidence: 67%

Determination of the Nucleic Acid Adducts Structure at the Nucleoside/Nucleotide Level by NMR Spectroscopy

Dračínský

Pohl

2015

Chem. Res. Toxicol.

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All living organisms are exposed to xenobiotics from the environment. The exposure can lead to the formation of covalent adducts of xenobiotics or their metabolites with nucleic acids (NAs).The knowledge of NA adduct structure provides valuable information n the mechanism of carcinogenesis on a molecular level. While NMR spectroscopy is extremely successful in structural analysis of many classes of molecules ranging from small inorganic and organic molecules to large biomacromolecules, the structural analysis of NA adducts by NMR spectroscopy is accompanied by some challenges. First, the structural diversity of the adducts is very large; the electrophilic species generated from the metabolism of xenobiotics can attack various atoms of the nucleobases, and new rings are frequently formed. The second challenge in the DNA adducts structure determination is the low sensitivity of NMR spectroscopy and low amount of the adducts isolated from in vivo experiments. Recent developments of NMR hardware and experimental methods have led, however, to unprecedented sensitivity. This contribution reviews NMR techniques that are commonly applied in the determination of nucleic acid adducts structure at the nucleoside/nucleotide level. These NMR techniques and the large structural heterogeneity of NA adducts are demonstrated on recent examples (mostly published after 2000) of NA adducts structure determined by NMR. Most of the examples report 2′-deoxyribonucles(t)ide derivatives, but RNA adducts are also briefly discussed. The influence of the formation of NA adducts on nucleoside conformation (particularly syn/anti orientation of the base) is also demonstrated on recent examples.

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Section: Recent Examples Of the Determination Of Na Adduct Structuresupporting

confidence: 67%

Determination of the Nucleic Acid Adducts Structure at the Nucleoside/Nucleotide Level by NMR Spectroscopy

Dračínský

Pohl

2015

Chem. Res. Toxicol.

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“…We assembled and tested a targeted library of structurally diverse guanine nucleoside phosphonates (see Supplementary Table 1 ) 34 35 36 37 38 . In this compound series – piperidine, pyrrolidine, prolinol, azetidine and acyclic phosphonates – the size of the heterocyclic amine ring is progressively smaller, decreasing from a six-membered ring to a linear molecule.…”

Section: Resultsmentioning

confidence: 99%

Molecular mutagenesis of ppGpp: turning a RelA activator into an inhibitor

Beljantseva

Kudrin

Jimmy

et al. 2017

Sci Rep

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The alarmone nucleotide (p)ppGpp is a key regulator of bacterial metabolism, growth, stress tolerance and virulence, making (p)ppGpp-mediated signaling a promising target for development of antibacterials. Although ppGpp itself is an activator of the ribosome-associated ppGpp synthetase RelA, several ppGpp mimics have been developed as RelA inhibitors. However promising, the currently available ppGpp mimics are relatively inefficient, with IC50 in the sub-mM range. In an attempt to identify a potent and specific inhibitor of RelA capable of abrogating (p)ppGpp production in live bacterial cells, we have tested a targeted nucleotide library using a biochemical test system comprised of purified Escherichia coli components. While none of the compounds fulfilled this aim, the screen has yielded several potentially useful molecular tools for biochemical and structural work.

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“…It is worth mentioning that the endocyclic nitrogen atoms of N-azanucleosides are conveniently protected since the N, N-acetals in N-azanucleosides, such as aza-thymidine (Figure 1), are prone to spontaneous hydrolysis. 11,[13][14][15][16][17][18][19] However, glycosidic C-C bonds are resistant to acidcatalyzed and enzymatic hydrolysis, making C-azanucleosides more stable. 20) In some cases, azaribofuranosyl moieties are replaced by chains containing nitrogen atoms, and these molecules are termed acyclic azanucleosides, such as aza-analogue of acyclovir (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

An Update Mini-Review on the Progress of Azanucleoside Analogues

et al. 2022

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The development of structurally novel nucleoside analogues is an active area in medicinal chemistry, since these drugs have proven clinical efficacy for decades.Azanucleosides are nucleoside analogues in which the sugar moieties are composed of nitrogen-containing rings or chains. In recent years, many azanucleosides have demonstrated therapeutic potential. In this short review, we describe recent advancements in azanucleosides, which may translate in a better understanding of the molecular design, biological activity, structure-activity relationship, and their related mechanism of action. The information summarized in this paper should encourage medicinal chemists in their future efforts to create more potent and effective chemotherapeutic agents.

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The Synthesis and Conformation of Dihydroxypiperidinyl Derivates of Nucleobases as Novel Iminosugar Nucleoside Analogs

Cited by 9 publications

References 31 publications

Determination of the Nucleic Acid Adducts Structure at the Nucleoside/Nucleotide Level by NMR Spectroscopy

Determination of the Nucleic Acid Adducts Structure at the Nucleoside/Nucleotide Level by NMR Spectroscopy

Molecular mutagenesis of ppGpp: turning a RelA activator into an inhibitor

An Update Mini-Review on the Progress of Azanucleoside Analogues

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