Water Ring Structure at DNA Interfaces: Hydration and Dynamics of DNA-Anthracycline Complexes

Lipscomb, Leigh Ann; Peek, Mary Elizabeth; Zhou, Fang; Bertrand, J. A.; VanDerveer, Donald; Williams, Loren Dean

doi:10.1021/bi00178a023

Cited by 93 publications

(66 citation statements)

References 30 publications

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“…Polygons similar to those described by other authors are found (28 -32). Pentagons predominate, but other polygons are also present, some of them clearly puckered, as found in other cases (32). Such a polygonal structure is reminiscent of that found in some forms of ice, although the most stable form of ice consists of six-membered rings of water molecules (33).…”

Section: Organization Of Counterions: An Ionic Crystal Around the Trimentioning

confidence: 80%

Solvent Organization in an Oligonucleotide Crystal

Soler-López¹,

Malinina²,

Subirana³

2000

Journal of Biological Chemistry

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We describe the crystal structure of d(GCGAATTCG) determined by x-ray diffraction at atomic resolution level (0.89 Å). The duplex structure is practically identical to that described at 2.05 Å resolution (Van Meervelt, L., Vlieghe, D., Dautant, A., Gallois, B., Pré cigoux, G., and Kennard, O. (1995) Nature 374, 742-744), however about half of the phosphate groups show multiple conformations. The crystal has three regions with different solvent structure. One of them contains several ordered Mg ؉2 ions and can be considered as an ionic crystal. A second region is formed by a network of ordered water molecules with a polygonal organization that binds three duplexes. The third region is formed by channels of solvent in which very few ordered solvent molecules are visible. The less ordered phosphates are found facing this channel. The latter region provides a view of DNA with highly movable charges, both negative phosphates and counterions, without a precise location.Two periods could be distinguished in the x-ray diffraction studies of DNA: the era of fiber diffraction of polymeric DNA/ polynucleotides and the time of single crystal x-ray structures of short fragments. The data available from fiber diffraction were limited and allowed no detailed analysis. The goal of DNA crystallography is, therefore, the study of detailed DNA structures. However, crystallographic data are also limited in some important aspects of DNA structure. For example, it is well known (1) that the solvent environment plays an important role in the conformational behavior and interactions of DNA. To study this feature in detail, it is necessary to work with x-ray data at atomic resolution level. Until recently, such data were available only for Z-DNA fragments. This situation is now changing. Synchrotron radiation of increasing power, together with better detectors and cryotechniques, make possible a third period of DNA crystallography: the epoch of high resolution DNA structures.We recently presented (2) a preliminary account of the structure of the B-DNA fragment (GCGAATTCG) solved at atomic resolution (0.89 Å). This structure had already been solved at 2.05-Å resolution (3, 4). In our previous analysis we described the water spine in the minor groove and compared it with related structures. Here we present a detailed analysis of the same oligonucleotide, which has multiple conformations in several parts of the phosphodiester backbone. We also describe the organization of the solvent, which in some regions shows well resolved water molecules, whereas in other regions it remains disordered, despite the fact that our crystals have been studied at 120 K. Thus, a frozen sample at atomic resolution, instead of showing a highly ordered duplex, demonstrates multiple conformations and regions of disordered solvent. MATERIALS AND METHODSCrystallization-The d(GCGAATTCG) nonamer was crystallized, using a batch method, in sitting drops containing 0.5 mM DNA duplex, 1 mM acridine-(Arg 4 ) drug-peptide aduct, 20 mM sodium cacodylate buffer, pH 7, 100 mM...

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Section: Organization Of Counterions: An Ionic Crystal Around the Trimentioning

confidence: 80%

Solvent Organization in an Oligonucleotide Crystal

Soler-López¹,

Malinina²,

Subirana³

2000

Journal of Biological Chemistry

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“…It has been reported that diVerent antitumor spectra between DR and DX might be caused by the structural diVerences in hydrogen-bonding networks produced from water molecules and either a DR-DNA or DX-DNA complex. DX contains a hydroxyl group at C-14 which forms the hydrogen-bonding to DNA phosphate, producing a conformational structure diVerent from that of DR and DNA (Neidle 1977;Quigley et al 1980;Pohle and Flemming 1986;Frederick et al 1990;Lipscomb et al 1994). The C-14 hydroxyl group may also be related to the ability of the drugs to accumulate especially in cell nuclei in vivo.…”

Section: Discussionmentioning

confidence: 99%

Differences in accumulation of anthracyclines daunorubicin, doxorubicin and epirubicin in rat tissues revealed by immunocytochemistry

Shin

Matsunaga

Fujiwara

2010

Histochem Cell Biol

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Although anthracycline antibiotics daunorubicin (DR), doxorubicin (DX), and epirubicin (ER) possess minor differences in their chemical structures, large differences are noted in their clinical use, as well as in cellular and plasma pharmacokinetic parameters in vivo. Immunocytochemistry for DR, DX, or ER was developed using an anti-DR monoclonal antibody (ADM-1-11), which has been demonstrated to react equally well with each of the three drugs, and therefore it was used for comparing their accumulation in several rat tissue cells after a single i.v. injection of each drug. In the kidney, immunoreactivity for each drug was distributed in essentially the same pattern and in the same strength 2 h after injection, but quite differently distributed in kidney cells thereafter, so that at 120-h post-injection significant amounts of DX and ER remained, but DR had almost completely vanished. Similar patterns of accumulation were observed in cells of other tissues including the pancreas, hair follicle, and stomach, with the exception of the intestine in which none of the three drugs remained after 120 h. These results appear to be supported by previous pharmacokinetic studies on the anthracyclines. The mechanism for such differences among the three drugs remains obscure, but the hydroxyl group at C-14 of DX and ER molecule might be related to the strong propensity of DX and ER to accumulate in tissue cells. The present results should contribute to the understanding of the mechanisms of the differences in the pharmacokinetics, as well as the possibly in anti-tumor activities of the anthracyclines.

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“…The latter two were a gift from the laboratory of Loren Williams at the Georgia Institute of Technology. The crystal structures for all three sequences are available from the literature: DNA 10 (15), DNA 6 (16), DNA 6 ·2D (17-19) and DNA 6 ·2A (18,19). All of the samples were warmed to room temperature after the 4 K irradiation and subsequently stored at ~−°C.…”

Section: Methodsmentioning

confidence: 99%

Direct Radiation Damage to Crystalline DNA: What is the Source of Unaltered Base Release?

2000

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The radiation chemical yields of unaltered base release have been measured in three crystalline double-stranded DNA oligomers after X irradiation at 4 K. The yields of released bases are between 10 and 20% of the total free radical yields measured at 4 K. Using these numbers, we estimate that the yield of DNA strand breaks due to the direct effect is about 0.1 μmol J −1 . The damage responsible for base release is independent of the base type (C, G, A or T) and is not scavenged by anthracycline drugs intercalated in the DNA. For these reasons, reactions initiated by the hydroxyl radical have been ruled out as the source of base release. Since the intercalated anthracycline scavenges electrons and holes completely but does not inhibit base release, the possibility for damage transfer from the bases to the sugars can also be ruled out. The results are consistent with a model in which primary radical cations formed directly on the sugar-phosphate backbone react by two competing pathways: deprotonation, which localizes the damage on the sugar, and hole tunneling, which transfers the damage to the base stack. Quantitative estimates indicate that these two processes are approximately equally efficient.

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Water Ring Structure at DNA Interfaces: Hydration and Dynamics of DNA-Anthracycline Complexes

Cited by 93 publications

References 30 publications

Solvent Organization in an Oligonucleotide Crystal

Solvent Organization in an Oligonucleotide Crystal

Differences in accumulation of anthracyclines daunorubicin, doxorubicin and epirubicin in rat tissues revealed by immunocytochemistry

Direct Radiation Damage to Crystalline DNA: What is the Source of Unaltered Base Release?

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