Electrochemical and ESR studies on Cu(II) complexes of bleomycin and its related compounds.

Ishizu, Kazuhiko; Murata, Shizuo; Miyoshi, Kiyonori; Takit, Tomohisa; Umezawa, Hamao

doi:10.7164/antibiotics.34.994

Cited by 20 publications

(11 citation statements)

References 12 publications

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“…These differences have been interpreted to be due to lack of a sixth ligand. 25 Thus, these studies are consistent with strong similarities between Cu(II)*P-3A and Cu(II)-BLM. Studies using S-band EPR and ENDOR spectroscopic methods, which should improve the resolution of the hyperfine coupling with ligands and better define the ligands, are also consistent with the conclusion that coordination chemistry of Cu(II)*BLM is analogous to that observed in Cu(II)-P-3A.…”

Section: Metal Complexes Of Blmsupporting

confidence: 83%

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Mechanisms of bleomycin-induced DNA degradation

Stubbe¹,

Kozarich²

1987

Chem. Rev.

898

643

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Section: Metal Complexes Of Blmsupporting

confidence: 83%

“…Recent attempts have been made using Xand S-band EPR and ENDOR spectroscopy to establish the similarities or differences between Cu(II)*P-3A and Cu(II)-BLM. [24][25][26][27][28] The results from these studies, in which a variety of different metals were coordinated to P-3A, BLM, and deglyco-BLM, are summarized in Table I.…”

Section: Metal Complexes Of Blmmentioning

confidence: 99%

Mechanisms of bleomycin-induced DNA degradation

Stubbe¹,

Kozarich²

1987

Chem. Rev.

898

643

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“…The formation of the two Cu(II)dPEP species on the DNA-fibers may reflect such a difference in the binding site. Ishizu et al have reported that the 3-O-carbamoyl group of the mannose moiety of the BLM molecule contributes to the stability of the metal site in the Cu(II)BLM complex by ligation at the sixth coordination site [26]. It has also been reported that comparisons of the best Co(II)-and Fe(II)-BLM models with the NMR-generated structures for some relevant metallo-BLMs favor the model with only endogenous ligands and N-carbamoyl ligation as the structure probably held in solution by both Co(II)-and Fe(II)-bleomycin [27].…”

Section: Cu(ii)dpepmentioning

confidence: 99%

Deglyco-peplomycin metal complexes on DNA fibers: a role of the sugar moiety for the stability and the orientation of the complexes

Iiyama¹,

Chikira²,

Oyoshi³

et al. 2003

J Biol Inorg Chem

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Binding structures of metal complexes of deglyco-peplomycin (dPEP) on DNA were investigated by comparing dPEP complexes with those of bleomycin (BLM) using DNA fiber EPR spectroscopy. A low spin species of Fe(III)dPEP observed in the DNA pellet changed irreversibly to several high spin species after the fabrication of the DNA fibers. The g values of the high spin species were different from those of Fe(III)BLM. The high spin species could not be nitrosylated reductively to ON-Fe(II)dPEP, suggesting that some nitrogen atoms coordinated to the Fe(III) were displaced on the DNA fibers. On the other hand, O(2)-Co(II)dPEP remained intact on the fibers similarly to O(2)-Co(II)BLM but with an increased randomness in the orientation on the DNA. In contrast to Cu(II)BLM, a considerable amount of Cu(II)dPEP bound almost randomly on B-form DNA fibers. These results indicated that the sugar moiety in peplomycin or bleomycin is playing an important role in enhancing the stability of the metal-binding domain and in the stereospecificity of the binding on DNA.

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“…Within this class are iso -PEPLM and iso -BLM A 2 with the carbamoyl substituent shifted from the 3- to the 2-hydroxyl group of the mannose sugar of PEPLM or BLM A 2 , respectively, as well as decarbamoyl-BLM A 2 for which the carbamoyl substituent has been eliminated. Electrochemical and EPR studies on Cu II BLM derivatives indicate that ligation at the sixth site by the O -carbamoyl group contributes to the stability of the complex ) addresses perturbations to the primary amine of the β-aminoalanine fragment: depyruvamide (DP)-PEPLM in which the β-aminoalamine moiety (and primary amine contained therein) is replaced with a H atom and N -acetyl-BLM A 2 in which the primary amine is made into a secondary amine through N -acetylation.…”

Section: Introductionmentioning

confidence: 99%

Spectroscopic Investigation of the Metal Ligation and Reactivity of the Ferrous Active Sites of Bleomycin and Bleomycin Derivatives

et al. 1998

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The geometric and electronic structures of high-spin ferrous complexes of bleomycin (FeIIBLM) and a series of systematically perturbed BLM derivatives have been investigated by optical absorption, circular dichroism (CD), and magnetic circular dichroism (MCD) spectroscopies. The active site of the unmodified drug complex is six-coordinate with the coordination sphere completed by at least five endogenous ligands including the pyrimidine, imidazole, deprotonated amide, and secondary and primary amine functionalities with either the 3-O-carbamoyl substituent of the mannose sugar or solvent bound at the sixth site. This weak sixth ligand is the exchangeable site of exogenous small molecule binding. Perturbing the carbamoyl substituent alters the coordination environment of the metal and decreases the azide binding affinities of the perturbed complexes. This is correlated with altered DNA cleaving capabilities. Additionally, altering the binding of the axial primary amine significantly affects the iron coordination sphere as evidenced by reduced π-back-bonding interactions specifically with the pyrimidine ligand. This pyrimidine π-back-bonding appears to play a key role in mediating the electron density localized on the ferrous center, which contributes to the unique oxygen chemistry and reactivity exhibited by FeIIBLM relative to other non-heme iron sites. Oxygen binding to derivatives in which the β-aminoalanine fragment has been removed leads to a high-spin ferric complex and no observed DNA strand scission, in contrast to the long-lived low-spin activated BLM intermediate that precedes DNA degradation.

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Electrochemical and ESR studies on Cu(II) complexes of bleomycin and its related compounds.

Cited by 20 publications

References 12 publications

Mechanisms of bleomycin-induced DNA degradation

Mechanisms of bleomycin-induced DNA degradation

Deglyco-peplomycin metal complexes on DNA fibers: a role of the sugar moiety for the stability and the orientation of the complexes

Spectroscopic Investigation of the Metal Ligation and Reactivity of the Ferrous Active Sites of Bleomycin and Bleomycin Derivatives

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