Three different cobalt complexes of bleomycin A2, B2, and Pepleomycin

Vos, Cornelis M.; Westera, G.

doi:10.1016/s0162-0134(00)80160-9

Cited by 8 publications

(3 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of laboratories prepared Co(III)-BLMs from Co(II), 02, and BLM; however, it was not until recently that the complex mixture of products produced were separated and partially characterized31, 124,127,130 (Scheme 11, Table XI). The Co(III)-BLMs are isolable with CM-Sephadex (ammonium formate elution) followed by reversed-phase HPLC.…”

Section: Co(iii)-blmmentioning

confidence: 99%

Mechanisms of bleomycin-induced DNA degradation

Stubbe¹,

Kozarich²

1987

Chem. Rev.

895

643

View full text Add to dashboard Cite

Section: Co(iii)-blmmentioning

confidence: 99%

Mechanisms of bleomycin-induced DNA degradation

Stubbe¹,

Kozarich²

1987

Chem. Rev.

895

643

View full text Add to dashboard Cite

“…Aerobic oxidation of Co(II)-BLM (Sugiura 1980) results in at least three stable products (DeRiemer et al 1979;Vos et al 1981;Albertini and Garnier-Suillerot 1982;Chang and Meares 1983) which are referred to as the BROWN, GREEN, and ORANGE Co(III)-BLMs. The spectral properties of the BROWN Co(III)-BLM Meares 1983, 1984) and Co(III)-pseudotetrapeptide A (Dabrowiak and Tsukayama 1981, pseudotetrapeptide A (2_) is the hydrolysis product of BLM which lacks the sugar and bithiazole moieties of the drug) suggest that BLM most probably employs five nitrogen donor centers located in the primary and secondary amines, pyrimidine and imidazole rings, and the peptide moiety next to the pyrimidine ring (in the boxed area in I to bind cobalt in these species).…”

Section: H O~nh2mentioning

confidence: 99%

Syntheses, structures and reactivities of designed analogues of cobalt(III)-bleomycinsz: Insight into the mechanism of sequence-specific DNA cleavage upon illumination

Farinas

Mascharak

1995

Proc. Indian Acad. Sci. (Chem. Sci.)

View full text Add to dashboard Cite

Three Co(III) complexes of a designed ligand PMAH that mimics the metal-binding domain of the antitumor antibiotic bleomycin (BLM) have been isolated and structurally characterized. The coordination structures of the various forms of Co(III)-BLMs have been established on the basis of spectral similarities between these synthetic analogues and the corresponding Co(III)-BLMs. All three analogues, like Co(III)-BLMs, induce DNA strand seission upon UV illumination. Both DNA cleavage and spin trapping experiments demonstrate that UV irradiation of the analogues generates a C/N-based radical on the ligand framework which rapidly reacts with water to produce "OH radical near the DNA helix and causes strand scission. A similar mechanism could account for the photoactivity of the CoflII)-BLMs. Covalent attachment of DNA-binding groups to these analogues enhances the DNA-aflinities and photocleavage efliciencies to a great extent. The hybrid analogues promote sequence-specific DNA photodamage at micromolar concentrations. The metallated cores of the hybrid analogues are the primary determinant of the observed sequence-specificity. Details of the mode of binding of the hybrid analogues to DNA have been explored by NMR techniques.

show abstract

“…Aerobic oxidation of a solution containing Co(II) salts and BLM affords several Co(III) chelates of the drug that are often referred to as ORANGE, BROWN, and GREEN Co III −BLM. − Spectroscopic studies have indicated that the cobalt(III) chelates of BLM most possibly employ five N donor centers located in the primary and secondary amines, the pyrimidine and the imidazole ring, and the peptide moiety adjacent to the pyrimidine. , The kinetically inert (low spin, d 6 system) Co III −BLMs bind to DNA quite strongly (10 6 −10 7 M -1 ) and do not cause any oxidative DNA damage like the Fe−BLMs. , However, Co III −BLMs cleave DNA when illuminated with UV 10,12 or visible light. Co III −BLMs photocleave DNA preferentially at pyrimidine residues located at the 3‘ side of guanines …”

Section: Introductionmentioning

confidence: 99%

Photoinduced DNA Cleavage Reactions by Designed Analogues of Co(III)−Bleomycin: The Metalated Core Is the Primary Determinant of Sequence Specificity

1996

View full text Add to dashboard Cite

A 2,4'-bithiazole group has been covalently attached to the Co(III) complex of a designed ligand PMAH that mimics the metal-binding locus of the antitumor drug bleomycin (BLM). The deprotonated PMA(-) ligand binds Co(III) via five nitrogens located in primary and secondary amines, a pyrimidine and an imidazole ring, and a peptide moiety. The 2,4'-bithiazole group is tethered to the [Co(PMA)](2+) unit via an imidazole that is connected to the bithiazole moiety with a (CH(2))(3) spacer. The structure of this hybrid analogue, namely, [Co(PMA)(Bit)]Cl(2) (7, Bit = 2'-methyl-2,4'-bithiazole-4-carboxamido-N'-(3-propyl)imidazole) has been established by spectroscopic techniques. 7 promotes photocleavage of DNA at micromolar concentrations. Unlike simpler analogues like [Co(PMA)(H(2)O)](2+) and [Co(PMA)Cl)](+) which induce random DNA cleavage upon UV illumination, 7 exhibits sequence specificity in the DNA photocleavage reaction. Intriguing is to note that 7 exhibits the same 5'GG-N3' sequence preference as another hybrid analogue [Co(PMA)(Int-A)]Cl(2) (6, Int-A = acridine-9-carboxamido-N'-(3-propyl)imidazole) that contains an acridine moiety as the DNA-binding group. The observed sequence specificity of 6 and 7 therefore does not reflect the sequence preferences of the DNA-binding groups (acridine and bithiazole). The results indicate that the metalated core of the hybrid analogues, i.e., the [Co(PMA)](2+) unit is the key factor in determining their sequence specificity.

show abstract

Three different cobalt complexes of bleomycin A2, B2, and Pepleomycin

Cited by 8 publications

References 7 publications

Mechanisms of bleomycin-induced DNA degradation

Mechanisms of bleomycin-induced DNA degradation

Syntheses, structures and reactivities of designed analogues of cobalt(III)-bleomycinsz: Insight into the mechanism of sequence-specific DNA cleavage upon illumination

Photoinduced DNA Cleavage Reactions by Designed Analogues of Co(III)−Bleomycin: The Metalated Core Is the Primary Determinant of Sequence Specificity

Contact Info

Product

Resources

About