Hydrolytic deamination reactions of amidine and nucleobase derivatives

2019 ◽  
Vol 120 (1) ◽  
Author(s):  
Kabir M. Uddin ◽  
Ahmad I. Alrawashdeh ◽  
David J. Henry ◽  
Peter L. Warburton ◽  
Raymond A. Poirier
Keyword(s):  
Hydrolytic Deamination

Artificial RNA Editing with ADAR for Gene Therapy

2020 ◽  
Vol 20 (1) ◽  
pp. 44-54 ◽  
Author(s):  
Sonali Bhakta ◽  
Toshifumi Tsukahara
Keyword(s):  
Gene Therapy ◽  
Genetic Code ◽  
Molecular Mechanism ◽  
Rna Editing ◽  
Comparative Studies ◽  
Genetic Diseases ◽  
Adenosine Deaminases ◽  
Family Protein ◽  
Hydrolytic Deamination

Editing mutated genes is a potential way for the treatment of genetic diseases. G-to-A mutations are common in mammals and can be treated by adenosine-to-inosine (A-to-I) editing, a type of substitutional RNA editing. The molecular mechanism of A-to-I editing involves the hydrolytic deamination of adenosine to an inosine base; this reaction is mediated by RNA-specific deaminases, adenosine deaminases acting on RNA (ADARs), family protein. Here, we review recent findings regarding the application of ADARs to restoring the genetic code along with different approaches involved in the process of artificial RNA editing by ADAR. We have also addressed comparative studies of various isoforms of ADARs. Therefore, we will try to provide a detailed overview of the artificial RNA editing and the role of ADAR with a focus on the enzymatic site directed A-to-I editing.

scholarly journals RNA editing in mesothelioma: a look forward

Open Biology ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 200112
Author(s):  
Ananya Hariharan ◽  
Suna Sun ◽  
Martin Wipplinger ◽  
Emanuela Felley-Bosco
Keyword(s):  
Rna Editing ◽  
Chronic Exposure ◽  
Cancer Growth ◽  
Biological Processes ◽  
Epigenetic Alterations ◽  
Rare Cancer ◽  
Public Data ◽  
Transcript Diversity ◽  
Transcriptional Process ◽  
Hydrolytic Deamination

RNA editing is a post-transcriptional process increasing transcript diversity, thereby regulating different biological processes. We recently observed that mutations resulting from RNA editing due to hydrolytic deamination of adenosine increase during the development of mesothelioma, a rare cancer linked to chronic exposure to asbestos. This review gathers information from the published literature and public data mining to explore several aspects of RNA editing and their possible implications for cancer growth and therapy. We address possible links between RNA editing and particular types of mesothelioma genetic and epigenetic alterations and discuss the relevance of an edited substrate in the context of current chemotherapy or immunotherapy.

Proton catalyzed hydrolytic deamination of cytosine: a computational study

2008 ◽  
Vol 120 (4-6) ◽  
pp. 429-435 ◽  
Author(s):  
V. Labet ◽  
A. Grand ◽  
C. Morell ◽  
J. Cadet ◽  
L. A. Eriksson
Keyword(s):  
Computational Study ◽  
Hydrolytic Deamination

scholarly journals The rate of hydrolytic deamination of 5-methylcytosine in double-stranded DNA

1994 ◽  
Vol 22 (6) ◽  
pp. 972-976 ◽  
Author(s):  
Jiang-Cheng Shen ◽  
William M. Rideout ◽  
Peter A. Jones
Keyword(s):  
Double Stranded Dna ◽  
Hydrolytic Deamination

scholarly journals Enzyme-mediated cytosine deamination by the bacterial methyltransferase M.MspI

1998 ◽  
Vol 332 (1) ◽  
pp. 223-230 ◽  
Author(s):  
Jean-Marc ZINGG ◽  
Jiang-Cheng SHEN ◽  
Peter A. JONES
Keyword(s):  
Dna Methyltransferases ◽  
Amino Group ◽  
Cytosine Deamination ◽  
Physiological Conditions ◽  
Solvent Water ◽  
Naturally Occurring ◽  
Haemophilus Parainfluenzae ◽  
Hydrolytic Deamination

Most prokaryotic (cytosine-5)-DNA methyltransferases increase the frequency of deamination at the cytosine targeted for methylation in vitro in the absence of the cofactor S-adenosylmethionine (AdoMet) or the reaction product S-adenosylhomocysteine (AdoHcy). We show here that, under the same in vitro conditions, the prokaryotic methyltransferase, M.MspI (from Moraxella sp.), causes very few cytosine deaminations, suggesting a mechanism in which M.MspI may avoid enzyme-mediated cytosine deamination. Two analogues of AdoMet, sinefungin and 5´-amino-5´-deoxyadenosine, greatly increased the frequency of cytosine deamination mediated by M.MspI presumably by introducing a proton-donating amino group into the catalytic centre, thus facilitating the formation of an unstable enzyme–dihydrocytosine intermediate and hydrolytic deamination. Interestingly, two naturally occurring analogues, adenosine and 5´-methylthio-5´-deoxyadenosine, which do not contain a proton-donating amino group, also weakly increased the deamination frequency by M.MspI, even in the presence of AdoMet or AdoHcy. These analogues may trigger a conformational change in the enzyme without completely inhibiting the access of solvent water to the catalytic centre, thus allowing hydrolytic deamination of the enzyme–dihydrocytosine intermediate. Under normal physiological conditions the enzymes M.HpaII (from Haemophilus parainfluenzae), M.HhaI (from Haemophilus hemolytica) and M.MspI all increased the in vivo deamination frequency at the target cytosines with comparable efficiency.

scholarly journals Efficiency of Galanti and Guisti Method of ADA Estimation in Comparison with the Gold Standard

2020 ◽  
Vol 30 (6) ◽  
Author(s):  
Manasa Reddy Dubba ◽  
Ramyashree V ◽  
Harshitha SS ◽  
Monalisa Biswas ◽  
Revathi P Shenoy ◽  
...  
Keyword(s):  
Gold Standard ◽  
Clinical Biochemistry ◽  
Assay Method ◽  
Sample Type ◽  
Manual Method ◽  
Medical College ◽  
Key Enzyme ◽  
Clinical Biochemistry Laboratory ◽  
The Cost ◽  
Hydrolytic Deamination

BACKGROUND: Adenosine Deaminase, the key enzyme of purine metabolism catalyzing the irreversible hydrolytic deamination of adenosine to inosine is implicated in a varied spectrum of human diseases ranging from SCID to TB and pneumonia. Estimation of ADA offers an easy, relatively affordable and reliable diagnostic alternative and/ or adjunct (specially in a TB endemic nation) which emphasizes the necessity of a feasible and implementable alternative method to the Diazyme method of ADA estimation requiring high end autoanalyzer and infrastructural setup.METHODS: Sixty body fluids samples (irrespective of gender, age, diagnosis or sample type) received by the Clinical Biochemistry Laboratory, Kasturba Medical College, Manipal for fluid ADA estimation by the Diazyme assay method (cobas 6000) was simultaneously processed by the Galanti and Guisti manual method to estimate the comparability and the aggregability of results obtained by the two analytical techniques.RESULTS: The Galanti and Guisti manual method of ADA estimation showed aggregability with the Diazyme autoanalyzer method for 90% of the assayed study samples with the manual method uniformly showing higher values when compared to the analyzer method. A correction factor of 2.44 was arrived at which could effectively achieve comparability between the two assay methods.CONCLUSION: The Galanti and Guisti manual method of ADA estimation might be a feasible, rapid, reliable and costeffective method for estimation of fluid ADA when compared to the cost and infrastructure intensive autoanalyzer.

scholarly journals Theoretical study of mechanisms for the hydrolytic deamination of cytosine via steered molecular dynamic simulations

RSC Advances ◽  
2018 ◽  
Vol 8 (61) ◽  
pp. 34867-34876 ◽  
Author(s):  
S. Tolosa ◽  
J. A. Sansón ◽  
A. Hidalgo
Keyword(s):  
Free Energy ◽  
Molecular Dynamic ◽  
Theoretical Study ◽  
Molecular Dynamic Simulations ◽  
Dynamic Simulations ◽  
Cytosine Deamination ◽  
Energy Profiles ◽  
Free Energy Profiles ◽  
Hydrolytic Deamination ◽  
Smd Simulations

Gibbs free energy profiles of the cytosine deamination assisted by a water molecule in a discrete aqueous medium were obtained by the application of Steered Molecular Dynamic (SMD) simulations.

Hydrolytic Deamination of 5-Methylcytosine in Protic MediumA Theoretical Study

2009 ◽  
Vol 113 (11) ◽  
pp. 2524-2533 ◽  
Author(s):  
Vanessa Labet ◽  
Christophe Morell ◽  
Jean Cadet ◽  
Leif A. Eriksson ◽  
André Grand
Keyword(s):  
Theoretical Study ◽  
Hydrolytic Deamination
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