Complexes between DNA and polyamines: a molecular model

Liquori, A. M.; Costantino, L.; Crescenzi, V.; D’Elia, Valerio; Giglio, E.; Puliti, R.; Savino, M.; Vitagliano, Vincenzo

doi:10.1016/0022-2836(67)90094-0

Cited by 267 publications

(124 citation statements)

References 8 publications

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“…These results could be expected on the basis of the more recent theoretical studies on the spermine-DNA interaction. In fact, whereas previous studies (Liquori et al, 1967) suggested a more favourable interaction of spermine within the minor groove of DNA, more recently Feuerstein et al (1990) proposed a model which supports the interaction with the major groove, based on both structural and energetic grounds.…”

Section: Discussionmentioning

confidence: 96%

Treatment with inhibitors of polyamine biosynthesis, which selectively lower intracellular spermine, does not affect the activity of alkylating agents but antagonizes the cytotoxicity of DNA topoisomerase II inhibitors

Desiderio

Bergamaschi²,

Mascellani³

et al. 1997

Br J Cancer

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Summary Inhibitors of ornithine decarboxylase (ODC), such as a-difluoromethylornithine (DFMO), may influence the cytotoxicity of anti-tumour agents that interact with DNA. Intracellular levels of putrescine and spermidine were markedly reduced by ODC inhibitors while the level of spermine, which is the main polyamine in nuclei, was unchanged. By combining a novel inhibitor of ODC, such as (2R, 5R)-6-heptyne-2,5-diamine (MDL 72.175, MAP), with an inhibitor of S-adenosylmethionine decarboxylase (SAMDC), such as 5'-{[(Z)-4-aminobut-2-enyl]methylamino}-5'-deoxyadenosine (MDL 73.81 1, AbeAdo), spermine was selectively depleted in a human ovarian cancer cell line OVCAR-3 (i.e. spermine became almost undetectable whereas the levels of spermidine and putrescine were not affected). The . The addition of spermine before drug treatment restored the sensitivity to the DNA topoisomerase 11 inhibitors, thus indicating that the reduced effect was related to the intracellular spermine level. The reason for the reduction in cytotoxicity is unclear, but it does not appear to be related to a cell cycle effect or to a decrease in the intracellular level of DNA topoisomerase 11. Drugs that modify polyamine biosynthesis are under early clinical development as potential new anti-tumour agents. These findings illustrate the need for caution in combining such drugs with DNA topoisomerase 11 inhibitors.

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Section: Discussionmentioning

confidence: 96%

Treatment with inhibitors of polyamine biosynthesis, which selectively lower intracellular spermine, does not affect the activity of alkylating agents but antagonizes the cytotoxicity of DNA topoisomerase II inhibitors

Desiderio

Bergamaschi²,

Mascellani³

et al. 1997

Br J Cancer

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“…Spd has been suggested to be important in regulation of protein synthesis (3,31) and the structure and/or function of DNA (24,28). Thus, in the aleurone layers of barley seeds, the level of Spd may affect the synthesis of a-amylase at transcriptional and/or translational levels.…”

Section: Methodsmentioning

confidence: 99%

“…Several lines of evidence indicate that polyamines may be involved in regulation of structure, function, and/or biosynthesis ofmacromolecules (10,16,24,28). In higher plants, polyamine metabolism has been related to the action of plant growth substances on regulation of plant growth and development (7, 8, 13, 22).…”

Section: Abstracrmentioning

confidence: 99%

“…Although the physiological roles of the amines have not yet been fully characterized, their syntheses and accumulation have been shown to be closely associated with all growth responses studied to date (1,12,32,36). Several lines of evidence indicate that polyamines may be involved in regulation of structure, function, and/or biosynthesis ofmacromolecules (10,16,24,28). In higher plants, polyamine metabolism has been related to the action of plant growth substances on regulation of plant growth and development (7,8,13,22).…”

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confidence: 99%

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Polyamine Metabolism and Its Relation to Response of the Aleurone Layers of Barley Seeds to Gibberellic Acid

Lin¹

1984

Plant Physiol.

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ABSTRACrPolyamine metabolism and its relation to the induction of a-amylase formation in the aleurone layers of barley seeds (Hordeum vulgare cv Himalaya) in response to gibberellic acid (GA3) has been investipted. A high-performance liquid chromatographic system has been employed for qualitative and quantitative analyses of putrescine (Put), cadaverine (Cad), spermidine (Spd), spermine (Spm), and agmatine (Agm).Active polyamine metabolism occurs in the aleurone cells of deembryonate barley half seeds during imbibition. The aleurone layers isolated from fully imbibed half seeds contain about 880 nanomoles of Put, 920 nanomoles of Spd, and 610 nanomoles of Spm as free form per gram tissue dry weight while the levels of Cad and Agm are relatively low. The polyamine levels do not change significantly in the aleurone layers in response to added GA3 (1.5 micromolar) during the 8-hour lag period of the growth substance-induced formation of a-amylase. Also, the polyamine levels are not altered by the presence of abscisic acid (3 micromolar) which inhibits the enzyme induction by GA3. Kinetic studies show that both applied IU-"Cqornithine and lU-'4Carginine are primarily incorporated into Put during 2 hours of incubation, but the incorporation is not significantly affected by added GA3. Additionally, added GA3 does not affect the uptake and turnover of 11, nor research (18,37,38). Experiments with the aleurone layers of barley seeds have shown a number of biochemical events related to the synthesis of a-amylase in response to added GA3. The mass synthesis of a-amylase begins 8 to 10 h after exposure of the tissue to the growth substance (9). Syntheses and accumulation of a-amylase mRNA (17) and ER (38) start as early as 2 to 4 h after treatment of the growth substance. For efficient expression of a-amylase gene(s), it has recently been suggested that a newly synthesized protein is required (26). If GA3 has effects on translation, the synthesis ofthe unidentified protein factor could occur shortly after addition of the growth substance. Thus, it would be interesting to investigate possible biochemical changes within 2 h after exposure of the aleurone layers to GA3, and to determine whether any changes are related to the effects of the growth substance on the transcriptional and/or translational events described.The diamine Put2 and polyamines Spd and Spm are ubiquitous in biological materials (1, 33,35 (1,12,32,36). Several lines of evidence indicate that polyamines may be involved in regulation of structure, function, and/or biosynthesis ofmacromolecules (10,16,24,28). In higher plants, polyamine metabolism has been related to the action of plant growth substances on regulation of plant growth and development (7, 8, 13, 22). In the internodes of light-grown dwarf peas the contents of Put and Spd per internode have been shown to increase during the elongation induced by exogenously applied GA3 (13). Also, it has been reported that the addition of GA3 results in 4-fold increase in the activity ofornithine decarboxyla...

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“…the positive charges are distributed at fixed. lengths along a conformationally flexible carbon chain, polyamines are not point-localized charges and are able to bridge critical distances [the distal ammonium charges in spermidine and spermine are separated, in the extended conformation, by 1.1 and 1.6 nm respectively (Liquori et al, 1967)]. These features allow specific interactions and functions, which are not shared by the metal cations.…”

Section: Introductionmentioning

confidence: 99%