Calicheamicins: discovery, structure, chemistry, and interaction with DNA

Lee, May D.; Ellestad, George A.; Borders, Donald B.

doi:10.1021/ar00008a003

Cited by 236 publications

(96 citation statements)

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“…2): a strand break consisting of 3Ј-phosphoglycolate-and 5Ј-phosphate-ended DNA fragments and base propenal; or a ketoaldehyde abasic site and free base (15). Calicheamicin and bleomycin have been shown to cause 4Ј-hydrogen atom abstraction (15,19,20). Calicheamicin is an enediyne antibiotic that, when activated by thiols, forms a minor groove-specific diradical species that abstracts deoxyribose hydrogen atoms (15,20).…”

Section: Resultsmentioning

confidence: 99%

Indirect mutagenesis by oxidative DNA damage: Formation of the pyrimidopurinone adduct of deoxyguanosine by base propenal

Dedon

Plastaras²,

Rouzer³

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

185

154

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Oxidation of endogenous macromolecules can generate electrophiles capable of forming mutagenic adducts in DNA. The lipid peroxidation product malondialdehyde, for example, reacts with DNA to form M 1 G, the mutagenic pyrimidopurinone adduct of deoxyguanosine. In addition to free radical attack of lipids, DNA is also continuously subjected to oxidative damage. Among the products of oxidative DNA damage are base propenals. We hypothesized that these structural analogs of malondialdehyde would react with DNA to form M 1 G. Consistent with this hypothesis, we detected a dose-dependent increase in M 1 G in DNA treated with calicheamicin and bleomycin, oxidizing agents known to produce base propenal. The hypothesis was proven when we determined that 9-(3-oxoprop-1-enyl)adenine gives rise to the M 1 G adduct with greater efficiency than malondialdehyde itself. The reactivity of base propenals to form M 1 G and their presence in the target DNA suggest that base propenals derived from oxidative DNA damage may contribute to the mutagenic burden of a cell.

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Section: Resultsmentioning

confidence: 99%

Indirect mutagenesis by oxidative DNA damage: Formation of the pyrimidopurinone adduct of deoxyguanosine by base propenal

Dedon

Plastaras²,

Rouzer³

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

185

154

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“…1; reviewed in refs. 22,[25][26][27]. In the present studies, we have employed an analog of calicheamicin ␥, calicheamicin Ø, in which the methyl trisulfide trigger has been replaced by a thioacetate group that undergoes hydrolysis in the absence of thiols (Fig.…”

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confidence: 99%

Supercoiling affects the accessibility of glutathione to DNA-bound molecules: Positive supercoiling inhibits calicheamicin-induced DNA damage

LaMarr

Nicolaou

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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DNA superhelical tension, an important feature of genomic organization, is known to affect the interactions of intercalating molecules with DNA. However, the effect of torsional tension on nonintercalative DNA-binding chemicals has received less attention. We demonstrate here that the enediyne calicheamicin ␥ 1 I , a strand-breaking agent specific to the minor groove, causes Ϸ50% more damage in negatively supercoiled plasmid DNA than in DNA with positive superhelicity. Furthermore, we show that the decrease in damage in positively supercoiled DNA is controlled at the level of thiol activation of the drug. Our results suggest that supercoiling may affect both the activity of nonintercalating genotoxins in vivo and the accessibility of glutathione and other small physiologic molecules to DNA-bound chemicals or reactions occurring in the grooves of DNA.Superhelical tension plays a role in many aspects of DNA physiology including transcription (1), replication (1), and repair (2). The genome of Escherichia coli has a net superhelical density () of ϷϪ0.05 (supercoils per helical turn), while there appears to be no net superhelical tension in the genomes of Drosophila melanogaster and humans (3). However, as a consequence of the loop organization of the genome in higher eukaryotes (4), transcriptionally active DNA contains high levels of localized torsional tension-negative in the 5Ј-ends and positive in the 3Ј-ends (5-11)-that is consistent with the twin-domain model of Liu and Wang (5) for transcriptionally induced DNA supercoiling. Though superhelical tension has well-defined effects on the interactions of proteins and small DNA intercalators, its effects on other molecules that interact with DNA have not been fully explored.The effects of torsional tension on small molecule-DNA interactions are a direct consequence of changes in DNA structure and dynamics. Negative and positive superhelical tension occur when the helix is unwound or over wound, respectively (12), and it has been estimated that as much as 30% of torsional tension is expressed in alterations of twist (helical repeat) with the remaining 70% expressed as writhing of the helix (13-15). Torsional tension has several consequences for DNA secondary structure, including formation of Z-DNA, cruciforms, and single-stranded regions (12,(16)(17)(18)(19). In the case of negatively supercoiled DNA, the under wound state of the helix favors binding of intercalating molecules because they induce local unwinding that is dissipated as global overwinding of the helix (9,20).By analogy to intercalators, the DNA interactions of other molecules that are sensitive to twisting and writhing of the helix should also be affected by superhelical tension. We have tested this hypothesis with the enediyne antibiotic calicheamicin ␥ (Fig. 1). The enediyne family is a structurally diverse group of DNA-damaging molecules that are cytotoxic at picomolar to femtomolar concentrations (21-23). This lethality is likely due to the production of high levels (Ͼ95%) of double strand...

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“…Recently, natural disaccharides and trisaccharides have attracted enormous attention. 3,4) A large number of oligosaccharides have been conjugated for new DNA-binding antitumor agents, 3) and specific ligands for cell-surface recognition 4) have been produced by chemical and enzymatic syntheses.We demonstrated that the reaction of D-glucose with cyclotriphosphate (P 3m ) afforded b-D-glucopyranosyl 1-triphosphate in good yield in a one-step process without protection of hydroxyl groups.5,6) Although D-glucose exists as an equilibrium mixture of a and b anomers under the reaction conditions, only b-D-glucopyranosyl 1-triphosphate was obtained stereoselectively. This method would be applicable to the phosphorylation of other monosaccharides.…”

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confidence: 99%

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confidence: 99%

Phosphorylation of Disaccharides with Inorganic cyclo-Triphosphate in Aqueous Solution.

2002

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Sucrose, maltose, and lactose are important disaccharides and cheap and valuable sources of renewable materials for industrial applications.1) For example, sucrose can be converted to ethanol, 2) which is widely used in various fields of industry and the source of C1 chemistry. Recently, natural disaccharides and trisaccharides have attracted enormous attention. 3,4) A large number of oligosaccharides have been conjugated for new DNA-binding antitumor agents, 3) and specific ligands for cell-surface recognition 4) have been produced by chemical and enzymatic syntheses.We demonstrated that the reaction of D-glucose with cyclotriphosphate (P 3m ) afforded b-D-glucopyranosyl 1-triphosphate in good yield in a one-step process without protection of hydroxyl groups.5,6) Although D-glucose exists as an equilibrium mixture of a and b anomers under the reaction conditions, only b-D-glucopyranosyl 1-triphosphate was obtained stereoselectively. This method would be applicable to the phosphorylation of other monosaccharides. 7,8) The phosphorylated products of oligo-and polysaccharides are expected to act as chiral selectors, 9) masking agents of metal ions, 10) and material for drug delivery systems (DDS). 11) Although this stereoselective phosphorylation is effective for monosaccharides, the existence of 1-OH is essential, which is not feasible in polysaccharides. It is more significant to apply this stereoselective phosphorylation reaction to disaccharides to open the way for the phoshorylation of oligo-and polysaccharides.In the present study, the reaction of cellobiose (1), lactose (2), maltose (3), sucrose (4), and a,a-trehalose (5) with P 3m was studied to develop selective phosphorylation of disaccharides in aqueous solution. Results and DiscussionPhosphorylation of Cellobiose (1), Lactose (2), and Maltose (3) with P 3m Reducing disaccharides used in the present study are shown in Chart 1. Phosphorylation was carried out essentially according to the previous method.6) Figure 1 shows the HPLC profiles for the reaction solution of cellobiose (1) (1.0 mol · dm Ϫ3) and P 3m (0.5 mol · dm Ϫ3) incubated at pH 12 at room temperature. The peak of the main product (6) appeared at a retention time of about 17 min. The yield of 6 increased with reaction time to reach the maximum yield of 28% after 78 h and then decreased gradually (Fig. 2).To identify product (6) in the phosphorylation of 1 with P 3m , 6 was isolated using anion-exchange resin (see Experimental). (Table 1) of 6 show two doublets (Ϫ11.8, Ϫ5.51 ppm) and one doublet of doublets (Ϫ20.6 ppm) characteristic of triphosphate derivatives. [6][7][8]12) Figure 3A shows the 31 P-NMR spectrum of the P a region in 6. The spectrum had one doublet of doublets at Ϫ11.8 ppm, which became a doublet on 1 H-decoupling, indicating the characteristic peak of P a in triphosphate deriva- November 2002Chem. Pharm. Bull. 50(11) 1453-1459 (2002) 1453 * To whom correspondence should be addressed. e-mail: mtsuhako@kobepharma-u.ac.jp © 2002 Pharmaceutical Society of Japan Phosphorylation...

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Calicheamicins: discovery, structure, chemistry, and interaction with DNA

Cited by 236 publications

References 64 publications

Indirect mutagenesis by oxidative DNA damage: Formation of the pyrimidopurinone adduct of deoxyguanosine by base propenal

Indirect mutagenesis by oxidative DNA damage: Formation of the pyrimidopurinone adduct of deoxyguanosine by base propenal

Supercoiling affects the accessibility of glutathione to DNA-bound molecules: Positive supercoiling inhibits calicheamicin-induced DNA damage

Phosphorylation of Disaccharides with Inorganic cyclo-Triphosphate in Aqueous Solution.

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