Active centre model on the structure and function of the bleomycin molecule as the prototype of esteratic enzymes

Murakami, Hideo; Mori, Hidefumi; Taira, Sadako

doi:10.1016/0022-5193(73)90240-3

Cited by 18 publications

(4 citation statements)

References 18 publications

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“…The subsequent increase in the strain and polarization of the /V-glycosidic bond probably results in an increase in the rate of spontaneous loss of bases from the DNA. This intercalation has been suggested previously (Murakami et al, 1973). The mechanism in the presence of sulfhydryl might involve a different portion of the BLM molecule (Murakami et al, 1973).…”

Section: Discussionsupporting

confidence: 64%

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Two actions of bleomycin on superhelical DNA

Ross¹,

Moses²

1978

Biochemistry

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Section: Discussionsupporting

confidence: 64%

“…This intercalation has been suggested previously (Murakami et al, 1973). The mechanism in the presence of sulfhydryl might involve a different portion of the BLM molecule (Murakami et al, 1973). The ß-hydroxyhistidine group is directed toward the ionized oxygen of the phosphate by an electrophilic attraction.…”

Section: Discussionmentioning

confidence: 51%

Two actions of bleomycin on superhelical DNA

Ross¹,

Moses²

1978

Biochemistry

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“…Both compounds lengthened linear DNA by 3.1 Á per molecule bound, and linear dichroism (303-315 nm) of bleomycin hound to linear DNA oriented in an electric field jBleomycin is an antitumor drug which produces single-and double-strand breaks in DNA (Suzuki et al, 1969;Haidle, 1971;Povirk et al, 1977) and releases free bases (Haidle et al, 1972;Müller et al, 1972). A free radical mechanism for these reactions (Sausville et al, 1976;Lown & Sim, 1977) and detailed enzyme-like mechanisms (Müller & Zahn, 1977;Murakami et al, 1973) have been proposed, but none have been either proven or ruled out. Bleomycin binds to both DNA and to divalent metal ions (Chien et al, 1977;Nunn, 1976;Sausville et al, 1976), and knowledge of the stereochemistry of these interactions could aid greatly in elucidating the reaction mechanism.…”

mentioning

confidence: 99%

Binding of bleomycin to DNA: intercalation of the bithiazole rings

Povirk¹,

Hogan²,

Dattagupta³

1979

Biochemistry

178

127

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At pH 5.5, binding of bleomycin relaxed supercoiled ColE1 DNA without breaking it. Binding of tripeptide S, a fragment of the drug containing the bithiazole rings, also relaxed and then recoiled supercoiled DNA, at pH 5.5 and at pH 8.0, where bleomycin is normally active. The unwinding angle was 12 degrees. Both compounds lengthened linear DNA by 3.1 A per molecule bound, and linear dichroism (303--315 nm) of bleomycin bound to linear DNA oriented in an electric field indicated the presence of a chromophore making an angle of 59--61 degrees with the helix axis. These results strongly suggest that bleomycin binding to DNA involves intercalation of the bithiazole rings. In 0.1 M Na Cl at pH 8, supercoiled ColE1 DNA was broken at a rate 50% greater than relaxed closed circular ColE1 DNA. Since supercoiling increases the affinity of DNA for intercalators, this result suggests that intercalative binding is involved in bleomycin-induced breakage of DNA.

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“…Bleomycin labeled with radioisotopes such as 57Co, 64Cu, 65Zn, 67Ga, 99mTc, 111 In, 169Yb, 197Hg, and 203Pb has been employed as a tumor scanning agent in the diagnosis and staging of a wide variety of solid tumors and malignant lymphomas (Monod and Rymer, 1973;Thakur, 1973;Kono et al, 1972; Renault et al, 1972). Models of the structures of BLM complexes with polyvalent cations and DNA have been proposed (Murakami et al, 1973(Murakami et al, , 1976.…”

mentioning

confidence: 99%

Proton nuclear magnetic resonance study of bleomycin in aqueous solution. Assignment of resonances

Chen¹,

Hawkins²,

Glickson³

1977

Biochemistry

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The 1H NMR spectrum of the glycopeptide antineoplastic antibiotic bleomycin has been examined in D2O solution (Fourier transform nuclear magnetic resonance, 270 MHZ) and in H2O solution (correlation nuclear magnetic resonance, 250 MHZ). Resonances have been assigned to specific hydrogens of the two most abundant congeners, bleomycin-A2 (BLM-A2) and bleomycin-B2 (BLM-B2), on the basis of (1) homonuclear spin decoupling, (2) comparison of the spectra of BLM-A2, BLM-B2, fragments of these antibiotics, and the related antibiotic phleomycin, and (3) the pH dependence of chemical shifts. Resonance assignments are presented for all the CH protons of BLM-A2 and BLM-B2 except for the saccharide groups, for which only the anomeric proton assignments are given. All of the NH protons have been identified with specific resonances except for the two primary amide groups, which yield four well-resolved peaks, whose specific assignment was not attempted. This study serves as a basis for future investigations of the conformation of bleomycin and its interaction with metals and nucleic acids.

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Active centre model on the structure and function of the bleomycin molecule as the prototype of esteratic enzymes

Cited by 18 publications

References 18 publications

Two actions of bleomycin on superhelical DNA

Two actions of bleomycin on superhelical DNA

Binding of bleomycin to DNA: intercalation of the bithiazole rings

Proton nuclear magnetic resonance study of bleomycin in aqueous solution. Assignment of resonances

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