Unusual conformational flexibility in N1‐substituted uncommon purine nucleosides Crystal structure of 1‐allyl‐isoguanosine and 1‐allyl‐xanthosine

@article{Liaw1992UnusualCF,
  title={Unusual conformational flexibility in N1‐substituted uncommon purine nucleosides Crystal structure of 1‐allyl‐isoguanosine and 1‐allyl‐xanthosine},
  author={Yen Chywan Liaw and Ji-Wang Chern and G S Lin and A. H.-J. Wang},
  journal={FEBS Letters},
  year={1992},
  volume={297}
}
Several new N1‐substituted uncommon purine nucleosides, including doridosine (1‐methyl‐isoguanosine; m‐iG), 1‐allyl‐isoguanosine (a‐iG) and 1‐allyl‐xanthosine (a‐X), have been synthesized and tested as agonists for the adenosine receptors. Some have smooth muscle relaxant or negative chronotropic activities. The X‐ray crystal structure of these compounds has been determined at atomic resolution in order to understand the structure‐activity relationship. The structures were solved by direct… 
Xanthine, xanthosine and its nucleotides: solution structures of neutral and ionic forms, and relevance to substrate properties in various enzyme systems and metabolic pathways.
TLDR
The acid/base properties of xanthine, its nucleosides and nucleotides, their N-alkyl derivatives and other analogues, and their relevance to studies on the foregoing are reviewed.
5,6-Diaminocytidine, a versatile synthon for pyrimidine-based bicyclic nucleosides.
This communication describes a convenient, facile, and high-yield synthesis of 3-(beta-D-ribofuranosyl)isoguanine and its 8-methyl derivative, as well as nucleoside analogues of pteridines, from a
A genetic view of the mitochondrial role in ageing: killing us softly.
TLDR
Accumulation of mitochondrial mutations with subtle functionality, which was overlooked by the mechanisms of selection, supplemented by slightly affected fusion-fission cycles, will hamper mitochondrial functional complementation within cells, disrupt mito-nuclear interactions and lead to ageing.
Mitochondrial DNA mutations in diseases of energy metabolism
  • D. Wallace
  • Biology, Medicine
    Journal of bioenergetics and biomembranes
  • 1994
TLDR
Maternally inherited mtDNA nucleotide substitutions range from neutral polymorphisms to lethal mutations, and somatic mutations appear to degrade cellular bioenergetic capacity, exacerbate inherited mitochondrial defects and contribute to tissue senescence.
Chapter 6 Pathophysiology of Mitochondrial Disease as Illuminated by Animal Models
TLDR
This chapter describes pathophysiology of mitochondrial disease as illuminated by animal models as amenable to detailed biochemical, physiologic, and molecular analysis and can be tested for promising therapies.
Method for in situ investigation of mitochondrial DNA deletions
TLDR
A sensitive method based on indirect in situ PCR is developed that is more sensitive than in situ hybridization for detecting the 4977 bp mtDNA deletion and it is demonstrated that the mutation does not occur uniformly among the cells of a given tissue/organ.
Mouse models for mitochondrial disease.
  • D. Wallace
  • Biology, Medicine
    American journal of medical genetics
  • 2001
TLDR
The role of mitochondrial ROS toxicity in disease and aging was confirmed by inactivating glutathione peroxidase (GPx1), resulting in growth retardation, and by total and partial inactivation of Mn superoxide dismutase (MnSOD; Sod2, resulting in neonatal lethal dilated cardiomyopathy and accelerated apoptosis in aging, respectively.
Deltoid human muscle mtDNA is extensively rearranged in old age subjects.
TLDR
It was suggested that the total extent of mtDNA mutation is very large in old age subjects and is sufficient to account for the decline in cellular COX activity with age and for a progressive decrease of overall mitochondrial bioenergetic capacity.
Mitochondrial defects in neurodegenerative disease.
  • D. Wallace
  • Biology, Medicine
    Mental retardation and developmental disabilities research reviews
  • 2001
TLDR
The bases for the genetic and phenotypic variability of mitochondrial diseases lie in the multiplicity of the mitochondrial genes dispersed across the human genome and the variety of cellular pathways and functions in which the mitochondria play a central role.
Aging and Degenerative Diseases
TLDR
The hypothesis is that many of the age-related degenerative diseases of humans as well as aging itself are related to defects in the mitochondrial bioenergetic pathway: oxidative phosphorylation (OXPHOS).
...
1
2
...

References

SHOWING 1-10 OF 18 REFERENCES
The Crystal Structure of Anhydrous Xanthosine Displays Intramolecular O(2′)H ... O(3′) Hydrogen Bond
Abstract From an equimolar dipeptide/xanthosine mixture in water/methanol, only the nucleoside crystallized in anhydrous form, space group P212121 with a = 17.406 (5) Å, b = 12.378 (4), c = 5.350 (2)
A novel and efficient synthesis of the naturally occurring nucleoside doridosine
Methylisoguanosine was synthesized by a one-pot reaction involving a condensation of 5-amino-l-(L3-D-ribofuranosyl)imidazole-4-carboxamide (1) with methyl isothiocyanate, treatment of the resulting
Synthesis and pharmacological evaluation of a series of analogues of 1-methylisoguanosine.
TLDR
In general, antiinflammatory activity paralleled the other results, except that the cyclic 3',5'-phosphate 17 was inactive at the dose tested, while the 3,5'-anhydronucleoside 14 was weakly active and displayed antiallergic effects.
Displacement of [3H] diazepam binding in rat brain by dipyridamole and by 1-methylisoguanosine, a marine natural product with muscle relaxant activity.
TLDR
Of a number of drugs known to interfere with purinergic systems, the adenosine uptake blocker dipyridamole was shown to be relatively potent as a diazepam displacer, with an IC50 of about 300 nM.
Enzymatic incorporation of a new base pair into DNA and RNA
The discovery of catalytic ribonucleic acid supports the hypothesis that an early form of life relied exclusively on RNA catalysis.’ We have suggested2 that one way of investigating the scope of RNA
Structure and function of A 1 adenosine receptors1
  • J. Linden
  • Chemistry, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1991
TLDR
The A1 adenosine receptor is the best characterized of the widely distributed purinergic receptor family and recent structure activity data suggest that subtypes of A1 (A1a, A1b, and A3) and A2 (A2a and A4) receptors may exist.
Purine receptors in mammalian tissues: pharmacology and functional significance.
  • M. Williams
  • Biology, Medicine
    Annual review of pharmacology and toxicology
  • 1987
TLDR
There is no evidence that specific anabolic processes form adenosine, distinct from those involved in its general metabolic functions, and the physiological factors regulating the extracellular availability of the nucleoside and its distribution make the development of a "purinergic"hesis of neuromodulation difficult.
1-Methylisoguanosine: an orally active marine natural product with skeletal muscle and cardiovascular effects.
Abstract 1-Methylisoguanosine is a marine natural product with skeletal muscle relaxant, hypothermic and cardiovascular effects following oral administration in mice and rats. The cardiovascular
Characterization of the A2 adenosine receptor labeled by [3H]NECA in rat striatal membranes.
TLDR
The regional distribution of [3H]NECA binding and the affinities of adenosine agonists and antagonists for inhibition of binding indicate that the site labeled by [3NECA belongs to the high affinity, or A2a, subclass of A2 receptor.
Stimulation of guinea-pig brain adenylate cyclase by adneosine analogues with potent pharmacological activity in vivo.
Abstract 1-Methylisoguanosine, a marine natural product with potent muscle-relaxant and cardiovascular actions in vivo , interacts directly with adenosine receptors in guinea-pig brain slices to
...
1
2
...