Fe (II)-chelates based on redox-active pyridoxal-betaines as C-centered radicals causing single- and double-strand scissions to DNA.
The ability of 1-[N-Ethoxycarbonylmethylpridoxylidenium]-2-[2'- pyridyl]hydrazine bromide code name - [L2.9 = L+,X-]-FE(II) chelate [L2-9-Fe(II)] to induce breaks both in the 43kb linear double-strand lambda phage DNA, and in the 4363 base pair supercoiled pBR322 plasmid DNA is herein described. Neither the free ligand nor FE(II) alone demonstrated any effect on the DNA. The cleaving ability is shown to occur instantaneously under strictly anaerobic conditions, either in the presence or absence of the enzyme catalase. It is also shown to be dose dependent. Thus, at lambda DNA:L2-9-Fe(II) molar ratio of 3.7:1.0, the linear DNA is randomly cleaved into fragments ranging from 23.1kb to 4.3kb, whereas at approximately 1:1 molar ratio, the range extends down to 2.5kb fragments. By contrast, at 1:2.7 [plasmid DNA]: chelate-Fe(II) molar ratio, a single-strand nick was observed, and a double strand break was noted at a 1:50 ratio [( plasmid DNA]: chelate-Fe(II). A multi-stage redox cycling involving a carbon-centered (L,X-)-Fe(III) radical capable of transferring an electron to the DNA to form high unstable [DNA].- anion-radical is invoked to explain the degradation of the chain macromolecule. Possible modes for regeneration of the chelate-Fe(III) radical both at the cell-free and at the cell levels are proposed.
Iheanacho
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EN
Kuvin Centre for the Study of Infectious and Tropical Diseases, Jerusalem, Israel.
Sarel
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S
Samuni
A
A
Avramovici-Grisaru
S
S
Spira
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DT
D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects; D004279:DNA, Viral / Q000187:drug effects; D005609:Free Radicals; D006834:Hydrazines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010957:Plasmids / Q000187:drug effects
D004277:DNA, Single-Stranded; D004279:DNA, Viral; D005609:Free Radicals; D006834:Hydrazines; D007502:Iron Chelating Agents; C065491:CGP 43902A