Nucleoside und Nucleotide als mögliche Therapeutika

Shen, T. Y.

doi:10.1002/ange.19700821804

Cited by 19 publications

(2 citation statements)

References 76 publications

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“…In particular this appears to be the case in aromatic esters or amides of AMP such as AMP-benzyl ester (H. Witzel and R. Pfeil, private communication) or AMP-imidazolide [38]. The extent to which this type of "stacking" interaction is realized in nucleosides and rnononucleotides remains to be determined; for adenosine derivatives of natural occurrence it appears insignificant at present.…”

Section: Non-classical Base Con Formationsmentioning

confidence: 99%

Adenine Nucleosides in Solution: Stabilisation of the anti‐Conformation by C‐5′ Substituents

Follmann

Gremels

1974

European Journal of Biochemistry

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Proton magnetic resonance spectra of 30 adenine nucleosides have been obtained in dilute (0.001 to 0.05 M) aqueous or dimethyl sulfoxide solutions and have been analysed with respect to structuredependent variations of the purine proton chemical shifts. In 2Hz0 the resonance signal of H-8 shows a marked dependence upon the nature of substituents linked to C-4' of adenine ribofuranoside derivatives and upon the presence of a 2': 3'-O-isopropylidene group while H-2 is relatively unaffected.Therefore the chemical shift difference, 6H-8 -6H-2 = Ad, may serve as an indicator of intramolecular ribose-base interact ons. d6 varies with the chemical nature of C-4' or C-5' substituents in the order: ammonium, sulfonium (0 ppm) < hydrogen < hydroxyl amino < thio < halogen < phosphate, carboxylate (0.4 ppm), and decreases with increasing chain length of these substituents. These results suggest the existence of electrostatic and dipolar repulsion or, in the majority of cases, attractive forces between the C-5' and C8-H regions of adenine nucleosides which have been previously demonstrated for 5'-nucleotides only. They imply a strong preference of most adenosine derivatives with unsubstituted 2' and 3'-hydroxyl groups for the anti-conformation range and the gauche, gauche C-5' conformation. In dimethyl sulfoxide, basically the same situation exists but different substituents exhibit smaller individual A6 variations than in water, indicating different solvation shells. In this solvent two additional conformation-stabilizing contributions can be recognized, viz. an interaction of the bridge oxygen (0-4') of ribose with adenine, and a hydrogen bond between H-8 and a 5'-carboxylate anion. This energetic stabilisation of the anti and g,g-conformers by most types of adenosine C-5' substituents supports the "rigidity" concept of nucleotides, extending it to the nucleoside level. The only exception found is 5'-nitromethyladenosine in which ultraviolet, circular dichroism and magnetic resonance spectra suggest rotation of the adenine base to a "non-classical" conformation due to base-chain n-electron interaction. The anti-conformation of the adenosine derivatives used in this study can in some cases be correlated with their enzymatic deamination by adenosine and AMP aminohydrolase.The biochemical function of nucleosides and nucleotides as substrates or effectors of the degrading and polymerizing enzymes of nucleic acid metabolism depends critically upon the molecular conformation which they assume in solution. The three substructures of a typical nucleoside, viz. the heterocyclic base, the pentofuranose ring and the exocyclic 5'-carbon atom carrying various substituents, are known to be arranged in certain relative orientations which have been Part 1 of a series entitled Forces Stabilizing the Conformation of Nucleosides in Solution.

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Section: Non-classical Base Con Formationsmentioning

confidence: 99%

Adenine Nucleosides in Solution: Stabilisation of the anti‐Conformation by C‐5′ Substituents

Follmann

Gremels

1974

European Journal of Biochemistry

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“…Shen [6] found some antiviral activity of compound 12 against parainfluenzavirus 3. A variety of other 5'-substituted 5-deoxyri-bofuranosyl purines and pyrimidines were synthesized and patented by Shen et al [7].…”

Section: Discussionmentioning

confidence: 99%

Derivatives of 3′-and 5′-Deoxyadenosine: Their Inhibitory Activity against DNA Viruses

1980

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3′-Deoxyadenosine, 3′-amino-3′-deoxyadenosine (3′3′), nine derivatives therefrom, two derivatives of 5′-amino-5′-deoxyadenosine and three derivatives of 3′, 5′-dideoxyadenosine were tested in cell culture for antiviral activity against three DNA viruses: adenovirus 5, herpesvirus hominis 1, and vaccinia virus. Cytotoxicity was also assessed. (3′3′) derivatives affected the multiplication of all three viruses similarly. Those which were effective were also cytotoxic at the same or slightly higher concentration. Substitution or other molecular modification of (3′3′) tend to lower the biological activity. The presence of an adenosine deaminase inhibitor enhanced both antiviral activity against adenovirus 5 and cytotoxicity in (3′3′) compounds, but not in the others. Both 5′-amino-5′deoxyadenosine compounds were active against vaccinia virus only. Of the three 3′, 5′-dideoxyadenosines, only one had both cytotoxic and antiviral activity. Most, if not all, seemingly antiviral effects appear to be caused by inhibition of the cell metabolism.

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Conformational studies of adenosine 5′‐phosphorodiamidates in aqueous solution

et al. 1984

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SynopsisCD and nmr studies show that the conformational equilibrium of' N(P)-alkylated adenosine 5'-phosphorodiamidates 2-4 and, t o a much lesser extent, adenosine 5'-phosphorodiamidate 1 differ at two parts from that of adenosine 5'-phosphate in water. The glycosidic bond conformation is slightly shifted into the direction of the syn range, and the ribose ring Nconformer population increases. The conformational changes increase with increasing degree of N(P)-alkylation and cause a change of the sign of the long-wavelength CD hand for 2-4.The new conformation may be characterized by a stacked arrangement for the adenine ring and the 5'-substituted phosphate group of 2-4. Hydrophobic attraction between the head and the tail of the molecules, as well as the entropy effect (which promotes the clustering of apolar faces in water), may be jointly responsible for this stacked arrangement. The intramolecular attractive forces stabilizing the stacked conformation may act at the expense of the solubility decreasing intermolecular attractive forces, and may thus he responsible for the increased water solubility of 2-4, which is higher than that of 1 by more than two orders of magnitude.

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Nucleoside und Nucleotide als mögliche Therapeutika

Abstract: In diesem Aufsatz werden Fortschritte bei Untersuchungen von

Cited by 19 publications

References 76 publications

Adenine Nucleosides in Solution: Stabilisation of the anti‐Conformation by C‐5′ Substituents

Adenine Nucleosides in Solution: Stabilisation of the anti‐Conformation by C‐5′ Substituents

Derivatives of 3′-and 5′-Deoxyadenosine: Their Inhibitory Activity against DNA Viruses

Conformational studies of adenosine 5′‐phosphorodiamidates in aqueous solution

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