Proton magnetic resonance studies of 2′-, 3′-, and 5′-deoxyadenosine conformations in solution

Westhof, Éric; Plach, H. J.; Cuno, I.; Lüdemann, H.‐D.

doi:10.1093/nar/4.4.939

Cited by 40 publications

(17 citation statements)

References 21 publications

(3 reference statements)

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“…At first sight, the gauche effect theory seems to account for all experimental data that have been obtained on nucleosides and nucleotides in solution. However, a substantial shortcoming is obvious, since the theory does not explain why the N @ S conformational equilibrium in 2'-deoxy nucleosides is virtually temperature independent (25). This experimental fact indicates that the free energy difference between the N and S states is in fact solely determined by entropy factors.…”

Section: Furanose Conformationmentioning

confidence: 95%

“…cordycepin) for the N pucker (24)(25)(26). At first sight, the gauche effect theory seems to account for all experimental data that have been obtained on nucleosides and nucleotides in solution.…”

Section: Furanose Conformationmentioning

confidence: 98%

“…The conformational properties of 2'-dA, an essential building block of DNA, have been studied extensively by means of X-ray crystallography (33) and nmr spectroscopy (25,(34)(35)(36). In the crystal structure, 2'-dA shows an N-type furanose ring (P = 14", v, = 35.5").…”

Section: '-Deoxyadenosine ('-Da)mentioning

confidence: 99%

“…The calculations were performed for a puckering amplitude of 35.5". The data points in the graph refer to literature data (25), as well as to our own experiments in D 2 0 in deuterated dimethyl formamide (see supplementary material). Clearly, the data points are clustered in the lower right region of the plot, indicating that the S form of the furanose ring is slightly preferred in solution.…”

Section: '-Deoxyadenosine ('-Da)mentioning

confidence: 99%

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Structural properties of modified deoxyadenosine structures in solution. Impact of the gauche and anomeric effects on the furanose conformation

Koole¹,

Buck²,

Nyilas³

et al. 1987

Can. J. Chem.

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A variable temperature high resolution ' H nuclear magnetic resonance study (at 300 or 500 MHz) of the two modified nucleosides 9-(2'-deoxy-P-D-threo-ribofuranosy1)-adenine (I) and 9-(3'-deoxy-P-D-threo-ribofuranosy1)-adenine (2) has been performed. It was found that the furanose conformation in 1 and 2 can be best described as a rapid North (N) South (S) equilibrium that is biased toward the N-form. For 1 , a marked temperature dependence of the N a S equilibrium was found, whereas the furanose conformation in 2 is virtually insensitive to temperature changes. Comparison of these results with the well-known conformational properties of the natural nucleosides 2'-deoxyadenosine (2'-dA) and 3'-deoxyadenosine (3'-dA) revealed that the net result of the gauche effect and the anomeric effect is of major importance in determining the furanose conformation. A brief discussion in terms of the thermodynamic parameters that govern the N a S equilibria in the investigated nucleosides is given.LEO H. KOOLE, HENK M. BUCK, AGNES NYILAS et JYOTI CHATTOPADHYAYA. Can. J. Chem. 65, 2089(1987.On a effectuC une Ctude de rCsonance magnktique nuclCaire a haute rCsolution (a 300 ou 500 MHz) et a tempkrature variable de deux nucltosides modifies, soit la (deoxy-2 P-D-thrio-ribofurannosy1)-9 adCnine (I) et la (dCoxy-3 P-D-thrio-ribofurannosy1)-9 adenine (2). On a trouvC que la meilleure faqon de dCcrire la conformation du furannose des composCs 1 et 2 fait appel a un Cquilibre rapide nord (N) a sud (S) dans lequel la forme N est favorisie. Dans le cas du composC 1 , on a observe que I'Cquilibre (N) a (S) est soumis ti une dkpendance marquee sur la tempkrature; par ailleurs, la conformation du furannose de la molCcule 2 est virtuellement insensible aux changements de temperature. Une comparaison de ces resultats avec les propriCtCs conformationnelles bien connues des nuclCosides naturels dCoxy-2' adCnosine (d-2' A) et dCoxy-3' adknoside (d-3' A) revkle que le resultat net de I'effet gauche et de l'effet anomerique est important dans la dktermination de la conformation du furannose.On prCsente une brkve discussion en fonction des paramktres thermodynamiques qui influencent I'Cquilibre (N) a (S) dans les nucltosides CtudiCs.[Traduit par la revue]

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Section: Furanose Conformationmentioning

confidence: 95%

Section: Furanose Conformationmentioning

confidence: 98%

Section: '-Deoxyadenosine ('-Da)mentioning

confidence: 99%

Section: '-Deoxyadenosine ('-Da)mentioning

confidence: 99%

See 2 more Smart Citations

Structural properties of modified deoxyadenosine structures in solution. Impact of the gauche and anomeric effects on the furanose conformation

Koole¹,

Buck²,

Nyilas³

et al. 1987

Can. J. Chem.

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“…during RNA synthesis results in termination of chain elongation (7,8). This activity has been well described in vitro with purified RNA polymerases and poly(A) polymerases from a number of organisms, including yeasts and mammals (9,10).…”

Section: Cordycepin Increases Sensitivity Of Hep3b Human Hepatocellulmentioning

confidence: 99%

Cordycepin increases sensitivity of Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis by inactivating the JNK signaling pathway

et al. 2013

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Abstract. Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis has been reported in various cancer cells. Cordycepin, a specific polyadenylation inhibitor, is the main functional component in Cordyceps militaris, which possesses many pharmacological activities including antitumor and anti-inflammation. In the present study, we demonstrated that treatment of cordycepin sensitized TRAIL-resistant Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis as evidenced by formation of apoptotic bodies, chromatin condensation and accumulation of cells in the sub-G1 phase. The induction of apoptosis following co-treatment with cordycepin and TRAIL in Hep3B cells appeared to be correlated with modulation of Bcl-2 family protein expression and activation of the caspase cascade, which resulted in the cleavage of poly(ADP-ribose) polymerase and β-catenin. In addition, cordycepin treatment also inhibited activation of c-Jun N-terminal kinase (JNK).Pretreatment with SP600125, a JNK inhibitor, resulted in a significantly increased sub-G1 population and caspase activity in cordycepin plus TRAIL-mediated apoptosis. Taken together, these results indicate that JNK acts as a key regulator of apoptosis in response to combined treatment with cordycepin and TRAIL in human hepatocellular carcinoma Hep3B cells.

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Bisubstrate Inhibitors of Catechol O‐Methyltransferase (COMT): the Crucial Role of the Ribose Structural Unit for Inhibitor Binding Affinity

et al. 2006

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Inhibition of the enzyme catechol O-methyltransferase offers a therapeutic handle to regulate the catabolism of catecholamine neurotransmitters, providing valuable assistance in the treatment of CNS disorders such as Parkinson's disease. A series of ribose-modified bisubstrate inhibitors of COMT featuring 2'-deoxy-, 3'-deoxy-, 2'-aminodeoxy-3'-deoxy-, and 2'-deoxy-3'-aminodeoxyribose-derived central moieties and analogues containing the carbocyclic skeleton of the natural product aristeromycin were synthesized and evaluated to investigate the molecular recognition properties of the ribose binding site in the enzyme. Key synthetic intermediates in the ribose-derived series were obtained by deoxygenative [1,2]-hydride shift rearrangement of adenosine derivatives; highlights in the synthesis of carbocyclic aristeromycin analogues include a diastereoselective cyclopropanation step and nucleobase introduction with a modified Mitsunobu protocol. In vitro biological evaluation and kinetic studies revealed dramatic effects of the ribose modification on binding affinity: 3'-deoxygenation of the ribose gave potent inhibitors (IC50 values in the nanomolar range), which stands in sharp contrast to the remarkable decrease in potency observed for 2'-deoxy derivatives (IC50 values in the micromolar range). Aminodeoxy analogues were only weakly active, whereas the change of the tetrahydrofuran skeleton to a carbocycle unexpectedly led to a complete loss of biological activity. These results confirm that the ribose structural unit of the bisubstrate inhibitors of COMT is a key element of molecular recognition and that modifications thereof are delicate and may lead to surprises.

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Proton magnetic resonance studies of 2′-, 3′-, and 5′-deoxyadenosine conformations in solution

Cited by 40 publications

References 21 publications

Structural properties of modified deoxyadenosine structures in solution. Impact of the gauche and anomeric effects on the furanose conformation

Structural properties of modified deoxyadenosine structures in solution. Impact of the gauche and anomeric effects on the furanose conformation

Cordycepin increases sensitivity of Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis by inactivating the JNK signaling pathway

Bisubstrate Inhibitors of Catechol O‐Methyltransferase (COMT): the Crucial Role of the Ribose Structural Unit for Inhibitor Binding Affinity

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