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Oxaliplatin | DNA/RNA Synthesis inhibitor | Read …



ABSTRACT/Summary:

Nucleoside reverse transcriptase inhibitors (NRTIs) have been hypothesized to inhibit mitochondrial DNA polymerase γ, resulting in decreased mtDNA synthesis and mitochondrial insufficiency in HIV-1- infected patients.

DNA synthesis inhibitors for the treatment of gastrointestinal cancer.

AB - The cell cycle specificity of chromatid breakage induced by inhibitors of DNA synthesis depends on the mechanism of drug action. 5-Hydroxy-2- formylpyridine thiosemicarbazone, hydroxyurea, and guanazole, compounds that inhibit ribonucleotide reductase, do not cause chromatid breakage during G 2 phase. In contrast, two active antitumor agents, arabinosylcytosine and 5-azacytidine, which are either incorporated into polynucleotides or affect DNA polymerase, produce chromatid breakage during Gg phase. All of these agents except guanazole also induce breakage in S phase.

Protein synthesis inhibitors - SlideShare

Processivity factors associate with DNA polymerases, enabling them to incorporate thousands of nucleotides without dissociating from the template. The processivity factors encoded by each of the herpesviruses are ideal targets for specifically blocking viral replication, particularly since they have unique primary amino acid sequences. Here we provide details of a rapid mechanistic plate assay and its potential application to high-throughput screening of libraries of tens of thousands of chemical compounds to identify inhibitors of processive DNA synthesis. Methods of validation testing are presented.

N2 - The cell cycle specificity of chromatid breakage induced by inhibitors of DNA synthesis depends on the mechanism of drug action. 5-Hydroxy-2- formylpyridine thiosemicarbazone, hydroxyurea, and guanazole, compounds that inhibit ribonucleotide reductase, do not cause chromatid breakage during G 2 phase. In contrast, two active antitumor agents, arabinosylcytosine and 5-azacytidine, which are either incorporated into polynucleotides or affect DNA polymerase, produce chromatid breakage during Gg phase. All of these agents except guanazole also induce breakage in S phase.

detailed note on protein synthesis inhibitors ..

Human malaria is one of the most devastating diseases caused by parasites of the genus of P/asmodium and transmitted to humans through the bites of infected anopheles mosquitoes. According to the latest estimates released in December 2013, there were about 207 million cases of malaria in 2012 and an estimated 627,000 deaths. 1Unlike higher eukaryotic cells which are capable of de nova purine synthesis, protozoan parasites rely predominantly on purine salvage from their host. Hypoxanthine-guanine phosphoribosyltransferase {HGPRT) and inosine-5'-monophosphate dehydrogenase {IMPDH) are the ubiquitous enzymes that catalyze key steps in the Plasmodium purine salvage pathway. Since purine and pyrimidine nucleotides are the basic building blocks of DNA and RNA as well as crucial components of other critical metabolic processes, guanine nucleotides are involved in many crucial cellular functions including transmembrane and intracellular signaling, DNA replication, and RNA synthesis, and thus are essential for cells' proliferation. As such, IMPDH and HGPRT can be exploited as potential target for the development of new therapeutics against human malaria. In fact, unlike IMPDH which has not yet been cloned, expressed and characterized from any of the P/asmodium species, HGPRT enzyme from this parasite is a well-established antimalarial drug target. 2� 3 The aim of this pilot project is to establish the foundation of a longterm biomedical research program within the Department of Chemistry and Physics at Southeastern Louisiana University, exploiting Plasmodium IMPDH and HGPRT as potential targets for the development of a new generation of antimalarial agents. As a proof of concept, a library of small molecules will be screened on these enzymes, with a goal of discovering new and selective inhibitors of Plasmodium IMPDH and/or HGPRT. Toward this goal, HGPRT will need to be expressed and purified, and the inhibition assays optimized, while IMPDH from Plasmodium will be cloned and expressed for the first time, and thus will need to be characterized before been used in assays. Furthermore, although HGPRT is a well studies and confirmed drug target in Plasmodium, 2� 3 only a handful of inhibitors have been developed so far, many of which are nucleoside_based. As a result, they act more as substrates, and thus are not very selective. This project aims to develop non-nucleoside-based inhibitors, with different electronic profiles and selective binding mechanisms.

The cell cycle specificity of chromatid breakage induced by inhibitors of DNA synthesis depends on the mechanism of drug action. 5-Hydroxy-2- formylpyridine thiosemicarbazone, hydroxyurea, and guanazole, compounds that inhibit ribonucleotide reductase, do not cause chromatid breakage during G 2 phase. In contrast, two active antitumor agents, arabinosylcytosine and 5-azacytidine, which are either incorporated into polynucleotides or affect DNA polymerase, produce chromatid breakage during Gg phase. All of these agents except guanazole also induce breakage in S phase.

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Answer to How are DNA synthesis inhibitors used to fight bioterrorism

Glen Research is delighted to introduce a GalNAc modification strategy using a monomeric GalNAc support and the equivalent GalNAc phosphoramidite. Our experimental work has shown that these products are fully compatible with regular oligonucleotide synthesis and deprotection. Oligonucleotides containing GalNAc can be deprotected using standard procedures during which the acetyl protecting groups on the GalNAc group are removed. Glen Research offers these GalNAc C3 products under an agreement with AM Chemicals LLC.

Inhibitors of repair DNA synthesis (pdf) | Paperity

Thus, a reliable method for measuring mtDNA synthesis could be useful in evaluating the role of NRTI-induced inhibition of mtDNA replication in the clinical syndrome.

GLS1 inhibitors selectively suppress DNA synthesis in ..



Here, we apply the 2H2O labeling method to test the hypothesis that NRTI agents inhibit mtDNA synthesis in vivo in rats, and we provide preliminary evidence for applicability of this method in humans.

What antibiotics inhibit DNA synthesis

The authors note that the detailed studies of the molecular mechanisms of DNA repair pathways were made possible by using site-specifically modified oligonucleotides and that the availability of phosphoramidites to synthesize oligonucleotides with DNA lesions has contributed to the field. They illustrate the article using primarily structural studies in the following examples:

these class of antibiotics are also protein synthesis inhibitors.

It should be noted that AZT is not one of the more potent inhibitors of mtDNA synthesis, compared with NRTIs such as stavudine (d4T) or didanosine (ddI).

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