Journal ArticleDOI
Enzymes of purine and pyrimidine metabolism from the human malaria parasite, Plasmodium falciparum.
Philip Reyes,Pradipsinh K. Rathod,Donald J. Sanchez,John E. K. Mrema,Karl H. Rieckmann,Hans-G. Heidrich,Hans-G. Heidrich +6 more
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TLDR
Two enzymes involved in the de novo synthesis of pyrimidines, orotic acid PRTase, and orotidine 5'-phosphate decarboxylase, were present in parasite extracts as were the enzymes for pyrimidine nucleotide phosphorylation.About:
This article is published in Molecular and Biochemical Parasitology.The article was published on 1982-05-01. It has received 200 citations till now. The article focuses on the topics: Purine nucleoside phosphorylase & Hypoxanthine.read more
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The Transcriptome of the Intraerythrocytic Developmental Cycle of Plasmodium falciparum
TL;DR: Analysis of the complete asexual intraerythrocytic developmental cycle (IDC) transcriptome of the HB3 strain of P. falciparum demonstrates that this parasite has evolved an extremely specialized mode of transcriptional regulation that produces a continuous cascade of gene expression, beginning with genes corresponding to general cellular processes, such as protein synthesis, and ending with Plasmodium-specific functionalities.
Journal ArticleDOI
Antimalarial drug discovery — approaches and progress towards new medicines
TL;DR: The cell-, chemistry- and target-based approaches used to discover new drug candidates that are currently in clinical trials or undergoing preclinical testing are discussed.
Journal ArticleDOI
Identification of a Metabolically Stable Triazolopyrimidine-Based Dihydroorotate Dehydrogenase Inhibitor with Antimalarial Activity in Mice
Ramesh Gujjar,Alka Marwaha,Farah El Mazouni,John H. White,Karen L. White,Sharon A. Creason,David M. Shackleford,Jeffrey Baldwin,William N. Charman,Frederick S. Buckner,Susan A. Charman,Pradip Rathod,Margaret A. Phillips +12 more
TL;DR: This study provides the first proof of concept that DH ODH inhibitors can suppress Plasmodium growth in vivo, validating DHODH as a new target for antimalarial chemotherapy.
Journal ArticleDOI
Triazolopyrimidine-based dihydroorotate dehydrogenase inhibitors with potent and selective activity against the malaria parasite Plasmodium falciparum
Margaret A. Phillips,Ramesh Gujjar,Nicholas A. Malmquist,John H. White,Farah El Mazouni,Jeffrey Baldwin,Pradipsinh K. Rathod +6 more
TL;DR: This study has identified the first nanomolar PfDHODH inhibitor with potent antimalarial activity in whole cells (EC50 = 79 nM) and the substituted triazolopyrimidine and its structural analogues were produced by an inexpensive three-step synthesis.
Journal ArticleDOI
Purine and pyrimidine transport in pathogenic protozoa: from biology to therapy.
TL;DR: Protozoan purine transporter-encoding genes characterised to date have been of the Equilibrative Nucleoside Transporter family conserved in a great variety of eukaryote organisms, but these protozoan transporters have been shown to be sufficiently different from mammalian transporter to mediate selective uptake of therapeutic agents.
References
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A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
TL;DR: This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr with little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose.
Journal ArticleDOI
Human malaria parasites in continuous culture
William Trager,James B. Jensen +1 more
TL;DR: Plasmodium falciparum can now be maintained in continuous culture in human erythrocytes incubated at 38 degrees C in RPMI 1640 medium with human serum under an atmosphere with 7 percent carbon dioxide and low oxygen.
Journal ArticleDOI
Ion-exchange chromatography of nucleotides on poly-(ethyleneimine)-cellulose thin layers☆
K. Randerath,E. Randerath +1 more
TL;DR: A great number of naturally occurring mononucleotides can be separated and identified by poly(ethyleneimine)-cellulose thin-layer chromatography by comparison with other present techniques for separating nucleotides.
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Tight-binding inhibitors-IV. Inhibition of adenosine deaminases by various inhibitors
TL;DR: Three ADA (adenosine deaminase) inhibitors, DHMPR, EHNA and deoxycoformycin (a transition state analog), were classified as readily reversible, semi-tight-binding and tight-binding inhibitors.
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