Calicheamicin−DNA Recognition:  An Analysis of Seven Different Drug−DNA Complexes

Kalben, Allison; Pal, Santona; Andreotti, Amy H.; Walker, Suzanne; Gange, David; Biswas, Kaustav; Kahne, Daniel

doi:10.1021/ja0005183

Cited by 15 publications

(13 citation statements)

References 33 publications

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“…This suggestion is consistent with the NMR results. [21][22][23][24][25] Experimental evidence from gel-cleavage studies indicating that the carbohydrate domain of the molecule is responsible for the observed site-specific binding and cleavage was first demonstrated by Drak et al, by comparing the cleavage efficiency of the DNA-bound synthetic aglycon calicheamcinone (6) with that of the DNA-bound intact antibiotic. 26 These researchers found that only 10% of the calicheamicinone molecules abstracted hydrogen from the DNA at a saturating binding concentration of 42 mM.…”

Section: Structural Features Of the Oligosaccharide Responsible For Tmentioning

confidence: 99%

“…All the published NMR studies agree that calicheamicin binds in the minor groove of DNA in an extended conformation with only minor modifications. [21][22][23][24][25] Sugar B binds edgewise deep within the walls of the minor groove as does the aromatic ring C residue with the iodine and orthomethyl group facing toward the bottom of the groove. The thiocarbonyl group linking sugar B to the aromatic C ring is orthogonal to the aromatic ring C as was observed in the X-ray crystal structure of the degradation product 11.…”

Section: Summary Of Structural Features Of the Calicheamicin-dna Complexmentioning

confidence: 99%

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Structural and conformational features relevant to the anti‐tumor activity of calicheamicin γ

Ellestad

2011

Chirality

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The structural and conformational features of the potent 10-membered enediyne-containing calicheamicin γ 1I that account for its remarkable DNA site-specific binding and cleavage are reviewed. A variety of spectroscopic and biophysical techniques were used to gain insight into the binding and stereospecific DNA cleavage of this potent antitumor agent. These include gel-shift cleavage assays, atom transfer NMR experiments, drug-DNA conformational studies, circular dichroism, and capillary electrophoresis. Computational descriptions are described for the DNA binding and cleavage of calicheamicin and its activated transient intermediates based on density functional and molecular mechanics calculations. In addition, the structure and clinical utility of calicheamicin immunoconjugates for antibody-targeted chemotherapy is presented.

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Section: Structural Features Of the Oligosaccharide Responsible For Tmentioning

confidence: 99%

Section: Summary Of Structural Features Of the Calicheamicin-dna Complexmentioning

confidence: 99%

Structural and conformational features relevant to the anti‐tumor activity of calicheamicin γ

Ellestad

2011

Chirality

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“…Sugar diol and amido alcohol arrangements are ''common features'' found in carbohydrates present in antibiotics and anticancer drugs [32,33] that interact with specific sequences of DNA in the minor groove. Their involvement in hydrogen-bonding interactions with the phosphate groups present in the groove has been postulated.…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Hydrogen Bonding Properties of a Series of Monosaccharides in Aqueous Media by 1H NMR and IR Spectroscopy

et al. 2002

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A technique, based on 1 H NMR and IR experiments, to characterise intramolecular hydrogen bonds in aqueous medium in a series of amino, amido and ammonium sugar derivatives has been established. Three groups of molecules, representing amides (4, 5 and 6), amines (7 and 8) and ammonium salts (chlorides 9 and 10, and phosphates 11 and 12), with different relative configurations of their functional groups, have been investigated to assess the effect of the nature and the stereochemistry of these groups on the hydrogen-bonding features of the sugar. The deduced features in water solution are compared to those obtained previously in nonpolar solvents. The phosphate salts of amines 7 and 8 (11 and 12)

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“…However, since the minor groove at these pyrimidine sequences is topologically diverse and contains different arrays of functional groups, the efforts to understand their mode of action did not produce clear and consistent results. Studies on calicheamicin bound to different DNA duplexes using NMR and biochemical cleavage data revealed that calicheamicin binds to all of the different sequences in the same mode (Kalben et al, 2000). The studies also proposed that calicheamicin binds to a range of oligopyrimidine sequences by the Fig.…”

Section: Calicheamicins and Esperamicinsmentioning

confidence: 93%

Disulfide and multisulfide antitumor agents and their modes of action

Lee

2009

Arch. Pharm. Res.

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A variety of natural products that contain disulfide or multisulfide bonds were found to display potent biological activities, including antitumor activities. At the center of these biological activities are disulfide or multisulfide moieties. The importance of disulfide or multisulfide groups in the areas of chemistry, biology, and pharmacology has been well recognized. Among these agents, especially noteworthy are mitomycin disulfides, leinamycin, thiarubrines, varacins, calicheamicins, and esperamicins. Their general features, including their biological profiles, peculiar structures, and related chemistries, were summarized and more importantly, their working mechanisms were elucidated in detail in this review. Mechanistic studies of these compounds have provided evidence of the key role of disulfide or multisulfide groups. In general, the cleavage of disulfide or multisulfide bonds produces thiol (or thiolate), which triggers an activation cascade leading to the generation of highly reactive electrophile(s) or cytotoxic species that may cause DNA strand scission. The main concerns with the mode of action are the reactivity and stability of disulfide and multisulfide bonds, their cleavage conditions, and the generation of toxic species. A range of studies for each agent was executed to gather important information on their activation, and the obtained information was gradually integrated to give some clues to the agents' working mechanisms. Such information may be further used to generate biomechanistically designed and more potent derivatives.

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Calicheamicin−DNA Recognition: An Analysis of Seven Different Drug−DNA Complexes

Cited by 15 publications

References 33 publications

Structural and conformational features relevant to the anti‐tumor activity of calicheamicin γ

Structural and conformational features relevant to the anti‐tumor activity of calicheamicin γ

Investigation of the Hydrogen Bonding Properties of a Series of Monosaccharides in Aqueous Media by 1H NMR and IR Spectroscopy

Disulfide and multisulfide antitumor agents and their modes of action

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