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Results for “Reverse Transcriptase Inhibitors”

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At least 19 recordsLinked to original sources
PubMed1977

Cytotoxic effect of a reverse transcriptase inhibitor, AF/ABDP cis, on ovaries of young Xenopus laevis--ultrastructural and autoradiographic study.

Observations with the light and electron microscopes showed that a reverse transcriptase inhibitor, AF/ABDP cis which is a rifampicin derivative, had a toxic effect on ovaries of young Xenopus laevis. It induced mitochondrial damage in all observed cells and marked alteration of the ultrastructure of nucleus of the pachytene oocyte. Light autoradiography showed that AF/ABDP cis caused wide variation in nuclear labelling with [3H] thymidine from one pachytene oocyte to another. Somatic cells were more uniformly labelled. These results are discussed in relation to the interpretation experiments upon eucaryote cells in which this drug is used as a reverse transcriptase inhibitor.

Animals↗
PubMed1977

Reverse transcriptase inhibitors and chemically induced bladder tumors in mice.

Recent immunologic and microbiologic evidence suggests that urothelial tumors may be caused by "C" type oncogenic viruses. Such viruses may exert their oncogenic potential in responce to stimulation by known chemical carcinogens. By means of a unique enzyme, reverse transcriptase, these viruses are able to incorporate genetic information into that of the host, and can thereby be transmitted vertically from generation to generation. An evaluation of the specific antiviral agents dimethylbenzyldemethl-rifampicin and streptovaricin-comples, which inhibit the enzyme reverse transcriptase, revealed no depay in the induction of bladder tumors by the chemical carcinogen, 2-formylamino-4-(5-nitro-2-furyl) thiazole (FANFT) in C3H mice. This observation suggests that the reproduction and release of virus may not be essential in the malignant transformation of bladder epithelial cells, but does not preclude the possiblity that inherited viral genetic information may be involved in the oncogenesis of bladder tumors.

Animals↗
PubMed1978

Gliotoxin analogues as inhibitors of reverse transcriptase. 2. Resolution and X-ray crystal structure determination.

A novel, simple, and efficient method for the chemical resolution of epidithiodioxopiperazines is reported, which is based upon covalent formation of diastereomers. This method might be a general one for the resolution of chiral cyclic disulfides. Dithiol 5, prepared from 2 by reduction with NaBH4, was allowed to react with the disulfenyl chloride 8 to yield 9 and 10, which were separated by short-column chromatography on silica gel. From these, the optically pure enantiomers 11 and 12, respectively, were obtained by reduction with NaBH4, followed by reoxidation with I2-pyridine. In this way the precursor 7 of the resolving agent could also be recovered. The absolute configurations of 11 and 12 were derived from CD spectra. Kinetic asymmetric transformation of the gliotoxin analogue 2 with the diphosphine 6 gave a 19% enrichment in one enantiomer of the starting material. Surprisingly, both enantiomers were found to inhibit reverse transcriptase, the RNA-dependent DNA polymerase, to the same degree, indicating that there is no relation between this property of epidithiodioxopiperazines and their bridgehead configurations. From the X-ray crystal structure determination it can be seen that there is a considerable torsional and conformational strain in compound 2, which might enhance the ease of cleavage of the S-S bond. A possible relationship between this property and the biological activity of 2 is discussed.

Anti-Bacterial Agents↗
PubMed1975

Revistin found by screening for inhibitors of reverse transcriptase of an oncogenic virus.

Revistin, a substance that strongly inhibits the reverse transcriptase activity of murine leukemia virus in our screening system, was obtained from a cultured broth of a soil streptomyces which was closely related to Streptomyces filipinensis. The assay method for the activity was based on the inhibition by a test material of the incorporation of 3H-dTMP into DNA synthesized by the reverse transcriptase of an oncogenic RNA virus. Crude revistin was isolated by serial procedures of salting out with ammonium sulfate and precipitation with cetylpyridinium chloride. The crude material showed neither antibacterial nor antifungal activity. It exhibited against splenomegaly in mice caused by Rauscher leukemia virus infection.

Animals↗
PubMed1978

Gliotoxin analogues as inhibitors of reverse transcriptase. 1. Effect of lipophilicity.

The reaction scheme, developed for the synthesis of the gliotoxin analogue 2, was found to be of general applicability for analogues with varying substituents at N(1) and C(2). Analogues 11b-g prepared by this method are inhibitors of reverse transcriptase (RNA-directed DNA polymerase). Their inhibitory activity seems to be related to the lipophilicity of the effector molecules: the most lipophilic compound is the most active inhibitor. The techniques of reversed-phase thin-layer chromatography with silylated, precoated plates as well as reversed-phase high-performance liquid chromatography were used to measure the relative lipophilicities; both techniques gave analogous results.

Anti-Bacterial Agents↗
PubMed1979

Rapid sequence determination of late simian virus 40 16S mRNA leader by using inhibitors of reverse transcriptase.

A method for the determination of the primary structure of spliced mRNA junction and leader sequences is described. By analogy to the DNA sequencing procedure of Sanger et al. [Sanger, F., Nicklen, S. & Coulson, A. R. (1977) Proc. Natl. Acad. Sci USA 74, 5463--5467], we use 2",3'-dideoxynucleoside triphosphates as chain-terminating inhibitors of the reverse transcriptase (RNA-dependent DNA polymerase) reaction. By using specific DNA restriction fragments as primers in combination with this technique, we have determined the sequence of the spliced junction between the body and the leader sequence of the 16S late mRNA of simian virus 40. The method described should be of general utility in mapping spliced mRNA regions for which the corresponding protein sequence (if any) is unknown.

Base Sequence↗
PubMed1978

[Molecular biological aspects of oncogenesis caused by RNA tumor viruses (author's transl)].

This article concerns the molecular mechanisms by which RNA tumor viruses, commonly called as oncornaviruses, transfer their genetic information from the genomic RNA (70 s RNA) of the virions to the cellular DNA, leading to neoplastic transformations. The article describes biochemical and serological properties of reverse transcriptase, its role in the life cycle of RNA tumor viruses and broader implications to molecular biology. In this connection, the authors report their own findings on the role of reverse transcriptase in a preleukemic disease, myelofibrosis. This enzyme, discovered in their laboratory, is antigenically closely related to reverse transcriptase of certain primate RNA tumor viruses, and of human leukemic cells. The article also describes the role of reverse transcriptase inhibitors in viral oncogenesis. Of particular interest, is the partially thiolated polycytidylic acid (MPC) which has been developed by the authors, and is known to have a very high binding affinity to the viral reverse transcriptase. The implication of these basic data on the clinical effectivity of MPC in human leukemia, documented in a few cases, has been discussed.

Cell Transformation, Neoplastic↗
PubMed1978

beta-Lapachone, an inhibitor of oncornavirus reverse transcriptase and eukaryotic DNA polymerase-alpha. Inhibitory effect, thiol dependence and specificity.

beta-Lapachone is a naturally occuring compound that can be isolated from a number of tropical trees. It is shown to be a potent inhibitor of reverse transcriptase activity from both avian myeloblastosis virus and Rauscher murine leukaemia virus. In addition, it affects eukaryotic DNA-dependent DNA polymerase-alpha activity: 50% inhibition is reached in 60-min incubation time by about 8 micron beta-lapachone. Enzyme activity is inhibited irrespective of the purity of the enzyme used or of the amount or type of template/primer or substrate present. The inhibitory effect of the drug is only observed in the presence of dithiothreitol. The primary site of action of beta-lapachone appears to be the enzyme protein, as is also borne out by the specificity of its action. Eukaryotic DNA-dependent DNA polymerase-beta, prokaryotic DNA-dependent DNA polymerase I, several other nucleic acid polymerases and some completely unrelated enzymes are not affected. Reverse transcriptase and DNA-dependent DNA polymerase-alpha may be in someway related in possessing similarly exposed '--SH structures' in their active sites. beta-lapachone thus affords a novel means of studying such interrelationships and of further characterizing enzymes.

Animals↗
PubMed1979

Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor viruses.

Suramin--a well-known antitrypanosomal agent--was found to exert a strong inhibitory effect on the RNA-directed DNA polymerase (reverse transcriptase) activity of several oncornaviruses such as Moloney murine leukemia virus, murine Rauscher leukemia viruses, Moloney murine sarcoma virus and avian myeloblastosis virus. Inhibition of enzyme activity was obtained with both endogenous viral RNA and (A)n . oligo(dT) as the template-primer. Suramin effected a 50% inhibition of the reverse transcriptase activity of oncornaviruses at a concentration range of 0.1--1 microgram/ml. In this aspect it compared favorably to ethidium bromide, another trypanocide drug which is considered as one of the most powerful inhibitors of oncornaviral DNA polymerases. The inhibition of reverse transcriptase activity by suramin was competitive with the template-primer, (A)n . oligo(dT), suggesting that the drug may interact with the template-primer binding site of the enzyme.

Avian Myeloblastosis Virus↗
PubMed2025

VANTAGE: van-based real-time HIV sequencing for transmission mapping and drug resistance profiling in war-affected Ukraine.

We deployed the VANTAGE (VAN for Transmissible Agent Genomic Epidemiology) mobile system in Lviv, Ukraine, demonstrating end-to-end sequencing of dried blood spot samples within a clinic van usually serving de-occupied and frontline regions. HIV-1 pol sequences were obtained from 50% of samples, all subtype A6. Median time to 100× coverage was 38 min. Phylogenetic analysis revealed a local transmission cluster including a displaced person and the non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutation E138A, supporting real-time HIV genomic surveillance in humanitarian crises.

Humans↗
PubMed1975

Oxime derivatives of erythromycin: inhibitors of Rous sarcoma virus reverse transcriptase activity and focus formation.

9-O-methyloximd erythromycin A and its analogue inhibited reverse transcriptase and blocked focus formation of Rous sarcoma virus. These chemicals inhibited neither DNA-dependent DNA polymerase nor DNA-dependent RNA polymerase from bacterial sources. However, they inhibited reverse transcriptase with an apparently differnt mechanism than that by rifamycin ABDP.

Animals↗
PubMed2024

Retrotransposons are co-opted to activate hematopoietic stem cells and erythropoiesis.

Hematopoietic stem cells (HSCs) and erythropoiesis are activated during pregnancy and after bleeding by the derepression of retrotransposons, including endogenous retroviruses and long interspersed nuclear elements. Retrotransposon transcription activates the innate immune sensors cyclic guanosine 3',5'-monophosphate-adenosine 5'-monophosphate synthase (cGAS) and stimulator of interferon (IFN) genes (STING), which induce IFN and IFN-regulated genes in HSCs, increasing HSC division and erythropoiesis. Inhibition of reverse transcriptase or deficiency for cGAS or STING had little or no effect on hematopoiesis in nonpregnant mice but depleted HSCs and erythroid progenitors in pregnant mice, reducing red blood cell counts. Retrotransposons and IFN-regulated genes were also induced in mouse HSCs after serial bleeding and, in human HSCs, during pregnancy. Reverse transcriptase inhibitor use was associated with anemia in pregnant but not in nonpregnant people, suggesting conservation of these mechanisms from mice to humans.

Animals↗
PubMedDate not supplied

The search for "virogene" in human prostatic tissues: prostatic DNA polymerases.

The "virogene-oncogene" hypothesis of Huebner and Todaro and the "provirus" hypothesis of Temin implicate RNA tumor viruses in the neoplastic transformation of mammalian cells. These hypotheses have been substantiated in several animal systems including primates and, presumably, in man. Because the detection in a tissue of one or two activities allegedly related to RNA tumor virus may not be conclusive evidence for viral presence, we have developed a scheme of coordinated morphologic, biologic, and biochemical investigations of human prostatic tissues. We report here the more recent progress we have made in one of the segments of our scheme of investigations. Two, possibly three, DNA polymerase activities from human prostatic tissue have been isolated and partially purified by DEAE-cellulose and phosphocellulose chromatography. These activities have been partially characterized. Based on template preferences and non-inhibition by selective inhibitors of reverse transcriptase, neither of the major polymerase activities appears to be the reverse transcriptase-type activity.

Adenine↗