Imidazo[1,2-c]pyrimidine nucleosides. Synthesis of N-bridgehead inosine monophosphate and guanosine monophosphate analogs related to 3-deazapurines

1975 ◽  
Vol 40 (25) ◽  
pp. 3708-3713 ◽  
Author(s):  
David G. Bartholomew ◽  
Phoebe Dea ◽  
Roland K. Robins ◽  
Ganapathi R. Revankar
Keyword(s):  
Guanosine Monophosphate ◽  
Inosine Monophosphate ◽  
Pyrimidine Nucleosides

scholarly journals The mycobacterial guaB1 gene encodes a guanosine 5'-monophosphate reductase with a cystathione-β-synthase domain

2021 ◽  
Author(s):  
Zdeněk Knejzlík ◽  
Michal Doležal ◽  
Klára Herkommerová ◽  
Kamila Clarova ◽  
Martin Klima ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
De Novo ◽  
Gene Knockout ◽  
Guanosine Monophosphate ◽  
Inosine Monophosphate Dehydrogenase ◽  
Purine Salvage ◽  
Inosine Monophosphate ◽  
Salvage Pathways ◽  
Cbs Domains ◽  
Purine Salvage Pathways

Purine metabolism plays a pivotal role in bacterial life cycle, however, regulation of the de novo and purine salvage pathways have not been extensively detailed in mycobacteria. By gene knockout, biochemical and structural analyses, we identified Mycobacterium smegmatis (Msm) and Mycobacterium tuberculosis (Mtb) guaB1 gene product as a novel type of guanosine 5'-monophosphate reductase (GMPR), which recycles guanosine monophosphate to inosine monophosphate within the purine salvage pathway and contains cystathione β-synthase (CBS) domains with atypical orientation in the octamer. CBS domains share a much larger interacting area with a conserved catalytic domain in comparison with the only known CBS containing protozoan GMPR and closely related inosine monophosphate dehydrogenase structures. Our results revealed essential effect of pH on allosteric regulation of Msm GMPR activity and oligomerization with adenine and guanosine nucleotides binding to CBS domains.Bioinformatic analysis indicated the presence of GMPRs containing CBS domains across the entire Actinobacteria phylum.

The raspberry locus of Drosophila melanogaster includes an inosine monophosphate dehydrogenase like coding sequence

Genome ◽  
1994 ◽  
Vol 37 (2) ◽  
pp. 333-344 ◽  
Author(s):  
D. Nash ◽  
S. Hu ◽  
N.-J. Leonard ◽  
S. Y. K. Tiong ◽  
D. Fillips
Keyword(s):  
Drosophila Melanogaster ◽  
Guanosine Monophosphate ◽  
P Element ◽  
Inosine Monophosphate Dehydrogenase ◽  
Ras Gene ◽  
Inosine Monophosphate ◽  
Lethal Mutations ◽  
Eye Colour ◽  
Lethal Allele ◽  
Monophosphate Dehydrogenase

DNA from the raspberry gene of Drosophila melanogaster has been cloned through P-element tagging of a dysgenically induced lethal allele. A transcribed DNA segment adjacent to the P insert encodes an amino acid sequence that is similar to known inosine monophosphate dehydrogenase (IMPDH) sequences. Further dysgenically induced lethals and all four known spontaneous ras eye-colour mutations have changes in the DNA either within or just upstream from the transcribed region. Identification of IMPDH as a probable product of the ras gene is compatible with the finding of an allele that requires dietary guanosine (GR), since the enzyme mediates the first of two biosynthetic steps leading from inosine monophosphate (IMP) to guanosine monophosphate (GMP). However, other auxotrophic mutants at the locus remain unexplained by the finding. The results further suggest that GMP synthesis from IMP is an essential process, despite the capacity of the fly for salvage synthesis of GMP from GR. Consideration of the phenotypes associated with mutants at the ras locus suggests that IMPDH activity is regulated in a tissue-specific manner.Key words: inosinate dehydrogenase, IMPDH, guanosine auxotrophy, purine synthesis, raspberry mutants, lethal mutations, Drosophila melanogaster.

THE EFFECT OF STRUCTURE ON NUCLEOSIDE KINASE ACTIVITY

1967 ◽  
Vol 45 (10) ◽  
pp. 1619-1632 ◽  
Author(s):  
K. J. Pierre ◽  
A. P. Kimball ◽  
G. A. LePage
Keyword(s):  
Divalent Cation ◽  
Kinase Activity ◽  
Ehrlich Ascites Carcinoma ◽  
Guanosine Monophosphate ◽  
Inosine Monophosphate ◽  
Ehrlich Ascites ◽  
Derivatives Of ◽  
Effect Of Structure

A study was made of the in vitro phosphorylation of some nucleosides in cell-free extracts from a thioguanine-resistant subline of Ehrlich ascites carcinoma which lacked inosine monophosphate – guanosine monophosphate pyrophosphorylase. The results indicated that there were kinases which catalyzed the phosphorylation of a variety of nucleosides. Ribofuranosyl-6-thiopurme was phosphorylated whereas the xylofuranosyl-, arabinofuranosyl-, and lyxofuranosyl-6-thiopurine were not substrates. The xylose and ribose derivatives of 6-methylthiopurine were phosphorylated but the arabinose derivative was not. Guanosine and some of its analogs were also phosphorylated but no correlation could be found between structure and phosphorylation of the guanosine analogs tested.The reaction showed dependence on the addition of divalent cation and an ATP-regenerating system.

scholarly journals PERBEDAAN PENGARUH ASUPAN KACANG TANAH (Arachis hypogaea) REBUS DAN PANGGANG TERHADAP KADAR ASAM URAT DALAM DARAH PADA WANITA DISLIPIDEMIA

2014 ◽  
Vol 3 (2) ◽  
pp. 278-284
Author(s):  
Fransiska Angelina ◽  
Kusmiyati DK ◽  
Yekti Wirawanni
Keyword(s):  
Arachis Hypogaea ◽  
Adenosine Monophosphate ◽  
T Test ◽  
Guanosine Monophosphate ◽  
Phosphoribosyl Pyrophosphate ◽  
Inosine Monophosphate ◽  
Post Test ◽  
True Experiment

LatarBelakang : Hiperurisemi dipengaruhi oleh keadaan dislipidemia dan asupan purin. Kondisi dislipidemia mengakibatkan menurunnya aktivitas enzim GA3PDH (Glyceraldehyde 3 phospate dehydrogenase) yang menyebabkan terjadinya diversi ribose-5-phospate menjadi PRPP (phosphoribosyl pyrophosphate). PRPP lalu ditransformasi menjadi inosine monophosphate (IMP). Dari senyawa perantara yang berasal dari adenosine monophosphate (AMP) dan guanosine monophosphate (GMP), purinic nucleotides digunakan untuk sintesis DNA dan RNA, dilanjutkan dengan  inosinyang kemudian akan mengalami degradasi menjadi hipoxantin, xantindan akhirnya menjadiasam urat. Asupan purin yang berlebihan seperti kacang tanah juga dapat meningkatkan kadar asam urat darah. Penelitianinibertujuanuntukmengetahuiperbedaan pengaruhasupan kacang tanah rebus dan panggang pada wanita dislipidemia.Metode : Jenis penelitian adalah true experiment dengan rancangan pre test – post test. Subjek adalah 22 wanita dislipidemia dengan kadar kolesterol LDL  ≥ 130 mg/dl,  HDL ≤ 40 mg/dl dan kadar asam urat normal 2,4-6,1 mg/dl. Subjek dibagi menjadi 2 kelompok dengan metode simple randomization, yang terdiri atas kelompok perlakuan pertama dan kelompok perlakuan kedua, masing-masing kelompok terdiri dari 11 subjek. Kelompok perlakuan pertama mendapatkan kacang tanah rebus sebanyak 77 gram/hari dan kelompok perlakuan kedua mendapatkan kacang tanah panggang sebanyak 77 gram/hari. Pemberian kacang tanah rebus dan panggang dilakukan selama 4 minggu. Uji normalitas menggunakan Shapiro Wilk. Analisis statistik menggunakan uji dependent t-test dan independent t-test.Hasil : Rerata kadar asam urat sebelum intervensi pada kelompok rebus yaitu 3,94 mg/dl dan pada kelompok panggang 4,45mg/dl. Rerata kadar asam urat  setelah intervensi pada kelompok rebus yaitu 4,79 mg/dl dan pada kelompok panggang 4,41mg/dl. Ada perubahan rerata kadar asam urat darah setelah diberikan kacang rebus (p=0,002). Tidak ada perubahan rerata kadar asam urat darah setelah diberikan kacang panggang (p=0,851).Kesimpulan : Ada perbedaan pengaruh konsumsi kacang tanah rebus dan panggang terhadap kadar asam urat darah pada wanita dislipidemia. Ada perubahan rerata kadar asam urat darah setelah diberikan kacang tanah rebus (p=0,002).

scholarly journals Enhancement of Nucleoside Production in Hirsutella sinensis Based on Biosynthetic Pathway Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Zhi-Qiang Liu ◽  
Bo Zhang ◽  
Shan Lin ◽  
Peter James Baker ◽  
Mao-Sheng Chen ◽  
...  
Keyword(s):  
Pathway Analysis ◽  
Biosynthetic Pathway ◽  
Differential Expression Analysis ◽  
Guanosine Monophosphate ◽  
Biosynthetic Pathways ◽  
Dihydroorotate Dehydrogenase ◽  
Inosine Monophosphate Dehydrogenase ◽  
Nucleotide Biosynthesis ◽  
Pyrimidine Nucleosides ◽  
Inosine Triphosphate Pyrophosphatase

To enhance nucleoside production in Hirsutella sinensis, the biosynthetic pathways of purine and pyrimidine nucleosides were constructed and verified. The differential expression analysis showed that purine nucleoside phosphorylase, inosine monophosphate dehydrogenase, and guanosine monophosphate synthase genes involved in purine nucleotide biosynthesis were significantly upregulated 16.56-fold, 8-fold, and 5.43-fold, respectively. Moreover, dihydroorotate dehydrogenase, uridine nucleosidase, uridine/cytidine monophosphate kinase, and inosine triphosphate pyrophosphatase genes participating in pyrimidine nucleoside biosynthesis were upregulated 4.53-fold, 10.63-fold, 4.26-fold, and 5.98-fold, respectively. To enhance the nucleoside production, precursors for synthesis of nucleosides were added based on the analysis of biosynthetic pathways. Uridine and cytidine contents, respectively, reached 5.04 mg/g and 3.54 mg/g when adding 2 mg/mL of ribose, resulting in an increase of 28.6% and 296% compared with the control, respectively. Meanwhile, uridine and cytidine contents, respectively, reached 10.83 mg/g 2.12 mg/g when adding 0.3 mg/mL of uracil, leading to an increase of 176.3% and 137.1%, respectively. This report indicated that fermentation regulation was an effective way to enhance the nucleoside production in H. sinensis based on biosynthetic pathway analysis.

scholarly journals Antiviral Activities of Mizoribine and other Inosine Monophosphate Dehydrogenase Inhibitors against Several Ortho- and Paramyxoviruses

1994 ◽  
Vol 5 (6) ◽  
pp. 366-371 ◽  
Author(s):  
Y. Kosugi ◽  
Y. Saito ◽  
S. Mori ◽  
J. Watanabe ◽  
M. Baba ◽  
...  
Keyword(s):  
Mycophenolic Acid ◽  
Measles Virus ◽  
Influenza Viruses ◽  
Guanosine Monophosphate ◽  
Host Cells ◽  
Inosine Monophosphate Dehydrogenase ◽  
Inosine Monophosphate ◽  
Antiviral Activities ◽  
Syncytial Virus

Mizoribine (4-carbamoyl-1-β-D-ribofuranosylimidazo-lelium-5-olate), EICAR (5-ethynyl-1-β-D-ribofuranosylimi-dazole-4-carboxamide), mycophenolic acid and ribavirin are antiviral agents targeted for inosine monophosphate (IMP) dehydrogenase. These compounds have been examined for their activities against orthomyxoviruses [influenza viruses (FluV)] and paramyxoviruses [parainfluenza viruses (PFIuV), mumps virus, measles virus (MLSV) and respiratory syncytial virus (RSV)] in vitro. Mizoribine was 1- to 9-fold more active than ribavirin against RSV, PFIuV and MLSV. EICAR and mycophenolic acid showed higher potency than mizoribine and ribavirin against all myxoviruses examined. None of the four compounds examined proved cytotoxic to stationary host cells (HeLa, Vero and MDCK) at a concentration of 200 μg ml−1 or more. On the other hand, EICAR and mycophenolic acid were toxic to rapidly growing cells at concentrations of 2.2-9 and 0.1-1.1 μg ml−1, respectively. Mizoribine and ribavirin showed cytotoxicity to the growing cells at higher concentrations (12-51 μg ml−1). The antiviral activities of mizoribine against FluV and RSV were reversed by 25-100 μm of each of guanosine and guanosine monophosphate (GMP). The antiviral activity of ribavirin against FluV was reversed by 25 μg of each of guanosine and GMP, while its activity against RSV was reversed by ≥ 100 μm of each of these compounds. Neither xanthosine nor xanthosine monophosphate (XMP) reversed the antiviral effects of mizoribine and ribavirin at concentrations of 300 μM. Concentrations 9 times higher than the median effective doses (EC50) of mizoribine and ribavirin inhibited the growth of RSV in HeLa cells as determined in an assay of infectious virus yield. Mizoribin should be further pursued as a candidate drug for the treatment of ortho- and paramyxovirus infections.

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