A conformational basis for the selective action of ara-adenine

Miles, Douglas L.; Miles, Daniel W.; Redington, Patrick; Eyring, Henry

doi:10.1016/0022-5193(77)90052-2

Cited by 20 publications

(7 citation statements)

References 37 publications

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“…However, it does not influence puckering modes which are still preferentially C 2 ,-endo or C 3 ,-endo and it has no obvious effect on the orientations about the exocyclic C 4 ,-C S ' and glycosyl Cl,-N bonds, which are preserved in the sc and anti ranges. The high-anti (-sc) orientation of the base, however, is forbidden, and this conformational characteristic could explain some of the biochemical properties of these nucleosides (649).…”

Section: Methodsmentioning

confidence: 99%

Principles of Nucleic Acid Structure

Saenger

1984

Springer Advanced Texts in Chemistry

5,985

312

6,279

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Section: Methodsmentioning

confidence: 99%

Principles of Nucleic Acid Structure

Saenger

1984

Springer Advanced Texts in Chemistry

5,985

312

6,279

View full text Add to dashboard Cite

“…The rationale for the selection of arabinosylnucleosides for this screening programme is the finding that they occur in a different glycosidic conformation from naturally occurring nucleosides (Miles et al 1977). From the knowledge that it is not the arabinosylnucleosides but the arabinosylnucleotides (e.g.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of Arabinofuranosylthymine in Non-infected and Herpesvirus (TK+ and TK-)-Infected Cells

Müller

Ζahn

Arendes

et al. 1979

Journal of General Virology

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SUMMARYThe phosphorylation of arabinofuranosylthymine (araThd) has been studied both in non-infected cells and in those infected with herpes simplex virus (HSV-I, Lennette; HSV-I, IES and HSV-2, D-316 ). In these experiments, HSV strains were used which either contain (Lennette, TK + and D-316 TK +) or lack (IES, TK-) the capacity to induce pyrimidine deoxyribonucleoside kinase. It was found that extracellularly administered araThd is phosphorylated to araTTP via araTMP and araTDP in both non-infected and in HSV-infected ceils. The phosphorylating capacity is more than tenfold lower in non-infected cells than in infected cells. Interestingly, cells infected with the TK-strain have a tenfold higher phosphorylating capacity than normal, uninfected cells, a fact which might indicate that host cell deoxythymidine kinase is induced during HSV infection. AraTMP is incorporated into cellular DNA but not into HSV DNA. This finding is in contrast to observations with arabinofuranosyladenine, which is incorporated into both cellular and HSV DNA. In vitro experiments with HSV-induced DNA polymerase show that araTTP strongly inhibits the enzyme activity. Therefore we conclude that the inhibition of HSV DNA polymerase by araTTP (formed intracellularly from araThd) is the explanation for the observed antiviral activity of araThd.

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“…A comparison of calculations on 2'-deoxyadenosine from two different sets of starting coordinates reveals that substantial glycosidic conformational effects can be attributed to ribose conformation (9,10). Polydeoxynucleotide duplexes are inactive as interferon inducers apparently because of conformational effects associated with removal of the 2'-OH group (4,5,15).…”

Section: Resultsmentioning

confidence: 99%

Interferon induction: a conformational hypothesis.

Miles¹,

Miles²,

Eyring³

1979

Proc. Natl. Acad. Sci. U.S.A.

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The ability of polynucleotides or polynucleotide duplexes such as poly (I).poly(C) to induce interferon production is proposed to depend on the existence of certain stable glycosidic orientations. It appears that a slight increase in instability of 1-3 kcal/mole (1 cal = 4.184 J) in the conformational regions near 200, 800, and 1600 leads to a loss of potency with respect to interferon induction. Thus, it is proposed that, for a lynucleotide to exist in the overall conformation necessary for interferon induction, stability of glycosidic orientations near 200, 800, and 1600 may be necessary to confer flexibility and activity on polynucleotide structures. This proposed conformational triad of stable conformational regions essential to interferon induction is based on the results of conformational energy calculations of the glycosidic rotational profiles of adenosine, 7-deazaadenosine, inosine, and 7-deazainosine, as well as the conformational properties of other purine nucleoside analogs, and on inferences derived from calculations about the conformational effect in polynucleotides of removing the 2'-OH group.

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A conformational basis for the selective action of ara-adenine

Cited by 20 publications

References 37 publications

Principles of Nucleic Acid Structure

Principles of Nucleic Acid Structure

Phosphorylation of Arabinofuranosylthymine in Non-infected and Herpesvirus (TK+ and TK-)-Infected Cells

Interferon induction: a conformational hypothesis.

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