Specificity of the 1-methyladenine receptors in starfish oocytes: synthesis and properties of some 1,8-disubstituted adenines, 1,6-dimethyl-1H-purine, and of the 1-(azidobenzyl)adenines

Mornet, R.; Leonard, Nelson J.; Theiler, Jane B.; Dorée, Marcel

doi:10.1039/p19840000879

Cited by 24 publications

(19 citation statements)

References 8 publications

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“…The combined filtrates were evaporated, and recrystallized from water to yield 75 mg (0.46 mmol, 87%) of white crystals. Analytical data are in agreement with those of Mornet et al [13].…”

Section: Experimental Procedures Reagentssupporting

confidence: 91%

“…The combined filtrates were evaporated, and recrystallized from water to yield 75 mg (0.46 mmol, 87%) of white crystals. Analytical data are in agreement with those of Mornet et al [13].8-Amino-1-methyladenine (29) was purified further by preparative HPLC (25X 1 cm, LiChrosorb RP select B, 7 pm, Merck, Darmstadt, Germany). It was eluted with 1% methanol, 20 mM triethylammonium formate pH 7.5 and appeared in signal 5. were characterized by FAB-or EI-MS, 'H-NMR and ultraviolet spectroscopy.…”

supporting

confidence: 85%

Section: Experimental Procedures Reagentssupporting

confidence: 74%

“…The solution was kept at 2°C overnight, and the yellow crystals that formed were collected by filtration to yield 0.42 g (2.2 mmol, 99%) of 8-azido-1 -methyladenine (28). Analytical data correspond to those provided by Mornet et al [13].For biological assay, a small amount of 8-azido-1-methyladenine was purified further by preparative HPLC (25 X 1 cm, LiChrosorb RP 18, 10 pm, Merck, Darmstadt, Germany) using 2% acetonitrile, 2 mh4 triethylammonium formate pH 5.5 as the eluting system. A by-pass was used between column and ultraviolet detector to protect the lightsensitive product.…”

mentioning

confidence: 78%

“…Analogues 28 and 29 act as l-methyladenine agonists. The observed weak activity of the 8-azido compound (28) could be due to a possible contamination with the very active 8-amino derivative (22) [13]. In this study we synthesized a highly purified 8-azido compound without any detectable contamination by B.…”

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confidence: 98%

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8‐Dimethylamino‐1‐methyladenine, a novel potent antagonist of the 1‐methyladenine receptor in starfish oocytes

Monsees

Meijer

Jastorff

1993

European Journal of Biochemistry

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Starfish oocytes are naturally arrested in the late G, phase of the first meiotic division. The follicle-cell-derived hormone, 1 -methyladenine, is responsible for highly synchroneous induction of oocyte maturation. A series of systematically modified 1-methyladenine analogues was used to map the essential molecular interactions between 1 -methyladenine and its stereospecific receptors, which are localized on the oocyte plasma membrane. The earlier hypothesis about structure/activity relationships has been confirmed. Quantum-chemical calculations indicated additional dipole -dipole interactions and presumably a charge-transfer interaction, with the nucleobase as n-electron donor. Among the 49 compounds tested, a series of novel inhibitors of 1-methyladenine-induced maturation was found. With the synthesis of 8-dimethylamino-1 -methyladenine (concentration for 50 % inhibition 1 pM), a very potent antagonist of the natural hormone was obtained which may become an important tool for investigating the mechanism of 1-methyladenine-induced maturation of the starfish oocytes, an important model for cell-cycle-control studies. The results are discussed in the context of preexisting biological data. In conclusion, we propose a modified model of the molecular interactions between 1-methyladenine and its receptor.Full grown starfish oocytes are arrested at the germinal vesicle stage during prophase of the first meiotic division. They resume meiosis when exposed to the natural hormone 1-methyladenine [l] which is produced by the follicle cells under the influence of a hormonal peptide of neural origin [2-41. Upon stimulation by 1-methyladenine, the oocytes undergo many morphological, biochemical, and physiological changes (for review see [5]).By their high synchrony and very rapid G,/M transition triggered by 1-methyladenine, starfish oocytes have become a major model to investigate the intracellular mechanisms which control the cell &vision cycle [6, 71. Nevertheless the pathway through which 1 -methyladenine leads to the activation of the P3kdc2/cy~lin WdCt3 kinase is largely unknown. It has been demonstrated [8 -101 that 1 -methyladenine controls meiosis by interacting with stereospecific receptors localized exclusively on the oocyte plasma membrane. From studies of structure/activity relationships [ 11 -131 for 1 -methyladenine analogues, it has been concluded that a lipophilic substituent on N-1, an amino group in the 6-position and a cationic charge are prerequisites for inducing activity. Any substitution in the 7-or 9-positions or a bulky 8-substituent is Abbreviations. CaFASW, calcium-free artificial sea-water; EGO, concentration for inducing SO% oocyte maturation; IC,,, dose for 50 % inhibition of 1 -methyladenine-induced maturation ; K$, relative lipophilicity ; HOMO, highest occupied molecular orbital ; LUMO, lowest unoccupied molecular orbital ; FAB-MS, fast-atom-bombardement mass spectroscopy ; (2H,)Me, SO, deuterated dimethylsulfoxide. detrimental to the interaction between the hormone and its receptor.Th...

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“…The combined filtrates were evaporated, and recrystallized from water to yield 75 mg (0.46 mmol, 87%) of white crystals. Analytical data are in agreement with those of Mornet et al [13].…”

Section: Experimental Procedures Reagentssupporting

confidence: 91%

supporting

confidence: 85%

Section: Experimental Procedures Reagentssupporting

confidence: 74%

mentioning

confidence: 78%

mentioning

confidence: 98%

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8‐Dimethylamino‐1‐methyladenine, a novel potent antagonist of the 1‐methyladenine receptor in starfish oocytes

Monsees

Meijer

Jastorff

1993

European Journal of Biochemistry

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Photochemical Generation of Iminoquinone Methides by 1,4-Hydrogen Migration in Derivatives of o-Tolylnitrene

Bucher

2001

Eur. J. Org. Chem.

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The photochemistry of a series of derivatives of o‐tolyl azide, bearing a variety of substituents in the benzylic positions, has been investigated using matrix isolation spectroscopy and density functional calculations. It has been found that introduction of any substituent possessing a lone pair (i.e., R = Br, Cl, MeO, Me2N) allows a 1,4‐hydrogen shift to take place, yielding iminoquinone methides. Additional methyl groups in the benzylic position, however, do not promote a photochemical conversion into iminoquinone methides. If the benzylic substituent itself is part of a ring system, the size of this ring plays an important role. Thus, 2‐methyl‐8‐nitrenotetrahydroisoquinoline rearranges very easily, whereas 4‐nitrenophthalan does not give the reaction. Density functional calculations [B3LYP/6‐31G(d)] have been used to gain an understanding of the reaction. It has been found that the activation energies depend strongly on the nature of the substituent, being lowest if R = NMe2. Incorporation of the benzylic substituent into a ring reduces the flexibility of the system and results in significantly raised barriers.

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References

1987

Chemistry of Heterocyclic Compounds: A Series of Monographs

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Specificity of the 1-methyladenine receptors in starfish oocytes: synthesis and properties of some 1,8-disubstituted adenines, 1,6-dimethyl-1H-purine, and of the 1-(azidobenzyl)adenines

Cited by 24 publications

References 8 publications

8‐Dimethylamino‐1‐methyladenine, a novel potent antagonist of the 1‐methyladenine receptor in starfish oocytes

8‐Dimethylamino‐1‐methyladenine, a novel potent antagonist of the 1‐methyladenine receptor in starfish oocytes

Photochemical Generation of Iminoquinone Methides by 1,4-Hydrogen Migration in Derivatives of o-Tolylnitrene

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