Mode of tilorone hydrochloride interaction to DNA and polydeoxyribonucleotides

Prakash, Chandra; Zunino, Franco; Gaur, V.; Zaccara, A.; Woltersdorf, M.; Luoni, Giuseppe; Götz, A.

doi:10.1016/0014-5793(72)80662-8

Cited by 38 publications

(13 citation statements)

References 6 publications

(4 reference statements)

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“…This is in accord with previously reported inhibitory effectiveness of these compounds [22,42]. These drugs are known to bind to DNA, presumably by intercalation [18,43]. Generally, fraction P1 appears more sensitive to various inhibitors than fraction P2 and nuclear polymerase.…”

supporting

confidence: 91%

DNA Polymerases of Rat Liver

Zunino

Gambetta

Colombo

et al. 1975

European Journal of Biochemistry

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Three distinct DNA-dependent DNA polymerase activitives have been partially purified from normal rat liver. Soluble activities are separable into two distinct fractions (P1 and P2) by phosphocellulose chromatography. A low-molecular-weight DNA polymerase was isolated from purified nuclei. The enzymes were characterized according to chromatographic and sedimentation behavior, enzymological properties, and response to various inhibitors. The results indicate that fraction P1 corresponds to the high-molecular-weight enzyme and suggest that polymerase P2 may be derived from partial dissociation of the high-molecular-weight enzyme. The molecular weight of polymerase P1 was estimated to be about 250000 by Sephadex column chromatography. Both fraction P2 and nuclear DNA polymerase appeared to be low-molecular-weight enzymes. However, the molecular size of these activities was apparently different. The estimated molecular weights of nuclear and P2 enzyme are about 40000 and 25000, respectively.As with the nuclear enzyme, polymerase P2 (but not P1) appeared to be free of detectable exonuclease activity. All of these polymerases showed a marked preference for initiated polydeoxyribonucleotide templates. The rat liver polymerases differed in their ability to use poly[d(A-T)] primer-template, as is shown by the ratios of their activity with this synthetic polymer to that with activated DNA: 0.5, 2.75, and 1.34 for P1, P2, and nuclear polymerase, respectively. Denatured DNA was a poor template for both enzymes P1 and P2, but it was inert as template for the nuclear enzyme.Although each of these polymerases required all four deoxynucleoside triphosphates for maximal activity, they catalyzed a high rate of synthesis in the absence of one or more deoxynucleoside triphosphates. Such a 'limited' synthesis was much more extensive for polymerase P2 and nuclear enzyme than for P1. Polymerase P1 was the most sensitive of the three to sulphydryl reagents, ethidium bromide, heparin, and single-stranded DNA. The responses of P2 and nuclear enzymes to various inhibitors were very similar. However, these two enzymes respond differently to heat and high ionic strength.The existence of multiple species of DNA polymerase has been demonstrated in a wide variety of eukariotic cells and tissues [1,2]. The extent and nature of multiplicity, the actual cellular localization, and the physiological function of enzyme activities are matters of current investigation. The eukaryotic DNA poly- ~ ~~Abbreviations. dNTPs, deoxyribonucleoside triphosphates; poly[d(A-T)], alternating double-helical deoxyadenylate-thymidylate copolymer; poly(dA) . (dT),,, polydeoxyadenylic acid associated with decathymidylic acid with a base-ratio of 1 : 1 : poly(rA) . (dT),,, polyadenylic acid associated with decathymidylic acid with a baseratio of 1 : 1 ; (dT),,, decathymidylic acid; poly(dA), polydeoxyadenylic acid.

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supporting

confidence: 91%

DNA Polymerases of Rat Liver

Zunino

Gambetta

Colombo

et al. 1975

European Journal of Biochemistry

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“…It has been reported earlier [6] that tilorone pre ferentially binds to the dAT regions of the DNA molecule. These studies were done by measuring the effect of tilorone on the melting (7',) of DNA preparations from various sources, having A-T content 28%-65%.…”

Section: Resultsmentioning

confidence: 89%

Influence of tilorone and cogeners on the secondary structure and template activity of DNA

Prakash

Woltersdorf

1974

FEBS Letters

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“…Tilorone antiviral activity is most likely due to a direct inhibition of viral DNA synthesis for both HSV-1 and VZV-infected cells [75,76,77,78]. Tilorone itself is mostly used as an antiviral agent as its hydrochloride.…”

Section: Resultsmentioning

confidence: 99%

Antiviral Activity of Metal-Containing Polymers—Organotin and Cisplatin-Like Polymers

et al. 2011

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Polymers containing platinum and to a lesser extent tin, have repeatedly demonstrated antitumor activity in vitro and in vivo against a variety of cell and tumor types. The mechanisms responsible for the antitumor activity include inducing a delay in cell proliferation and sister chromatid exchanges blocking tumor growth. As most DNA and some RNA viruses require, and even induce, infected cells to initiate DNA replication and subsequent cell division, compounds with antitumor activity will very likely also possess antiviral activity. This article examines the use of metal-containing polymers as a novel class of antivirals.

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Mode of tilorone hydrochloride interaction to DNA and polydeoxyribonucleotides

Cited by 38 publications

References 6 publications

DNA Polymerases of Rat Liver

DNA Polymerases of Rat Liver

Influence of tilorone and cogeners on the secondary structure and template activity of DNA

Antiviral Activity of Metal-Containing Polymers—Organotin and Cisplatin-Like Polymers

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