Reaction of anthramycin with deoxyribonucleic acid

Kohn, Kurt W.; Spears, Carlos

doi:10.1016/0022-2836(70)90008-2

Cited by 65 publications

(29 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is therefore interesting to ®nd out whether this is due to its in¯uence on hydrolysis. On the other hand, phosphates have been considered to act as a catalyst for this type of reaction [20]. The in¯uence of these parameters on the hydrolysis was studied but no signi®cant effects were observed.…”

Section: Hydrolysis Of Amementioning

confidence: 99%

Electrochemical Analysis of Anthramycin: Hydrolysis, DNA-Interactions and Quantitative Determination

2000

View full text Add to dashboard Cite

In aqueous solution, anthramycin methyl ether (AME), anhydroanthramycin (an imino form) and anthramycin are in equilibrium. It is found that anhydroanthramycin is electrochemically active. The AME hydrolysis reaction is studied by cyclic voltammetry. The kinetics of the DNA‐drug reaction is followed by AdTSV and it is found that the slowness of the interaction is due to anthramycin changes which take place in solution independently of the DNA presence. DPP is used as a sensitive method for the quantitative determination of the drug and a detection limit of 70 nM is obtained.

show abstract

Section: Hydrolysis Of Amementioning

confidence: 99%

Electrochemical Analysis of Anthramycin: Hydrolysis, DNA-Interactions and Quantitative Determination

2000

View full text Add to dashboard Cite

show abstract

“…The modified DNA was purified by ethanol precipitation and 5-20% sucrose gradient centrifugation. The reaction of anthramycin with DNA is accompanied by a gradual change in the anthramycin absorption peak (43), which shifts from 333 to 343 nm and decreases in amplitude (Fig. 2D).…”

Section: ј-Gatctccggattaggcccgggcmentioning

confidence: 99%

“…These different responses of the two M13 DNA fragments confirmed that the competition between M13 substrate and damaged pUC19 was selective for NER factors. is accompanied by a change in the anthramycin absorption peak, which shifted from 333 to approximately 340 nm and decreased in amplitude (43). The frequency of anthramycin modification of DNA (11.9 adducts/pUC19) was calculated from the absorbance at 321 nm (the maximum of the difference spectrum) and at 349 nm (the isosbestic point).…”

Section: Ner Substrate For Repair Competitionmentioning

confidence: 99%

Recognition of DNA Adducts by Human Nucleotide Excision Repair

Gunz

Heß

Naegeli

1996

Journal of Biological Chemistry

186

147

View full text Add to dashboard Cite

The mechanism by which mammalian nucleotide excision repair (NER) detects a wide range of base lesions is poorly understood. Here, we tested the ability of human NER to recognize bulky modifications that either destabilize the DNA double helix (acetylaminofluorene (AAF) and benzo[a]pyrene diol-epoxide (BPDE) adducts, UV radiation products) or induce opposite effects by stabilizing the double helix (8-methoxypsoralen (8-MOP), anthramycin, and CC-1065 adducts). We constructed plasmid DNA carrying a defined number of each of these adducts and determined their potential to sequester NER factors contained in a human cell-free extract. For that purpose, we measured the capacity of damaged plasmids to compete with excision repair of a site-directed NER substrate. This novel approach showed differences of more than 3 orders of magnitude in the efficiency by which helix-destabilizing and helixstabilizing adducts sequester NER factors. For example, AAF modifications were able to compete with the NER substrate ϳ1740 times more effectively than 8-MOP adducts. The sequestration potency decreased with the following order of adducts, AAF > UV BPDE > 8-MOP > anthramycin, CC-1065. A strong preference for helix-destabilizing lesions was confirmed by monitoring the formation of NER patches at site-specific adducts with either AAF or CC-1065. This comparison based on factor sequestration and repair synthesis indicates that human NER is primarily targeted to sites at which the secondary structure of DNA is destabilized. Thus, an early step of DNA damage recognition involves thermodynamic probing of the duplex. Nucleotide excision repair (NER)1 is an essential pathway for removing bulky base modifications from DNA. This repair mechanism involves endonucleolytic cleavage at two phosphodiester bonds, one 3Ј and the other 5Ј of the site of damage, followed by excision of DNA damage as the component of a single-stranded fragment (1-5). The excised oligonucleotide is replaced by DNA repair synthesis, and DNA continuity is reestablished by ligation. In mammalian cells, the major sites of incision are at the 5th phosphodiester bond 3Ј and the 24th phosphodiester bond 5Ј to the lesion (6).

show abstract

“…The sibiromycin-DNA complex is most stable to acid conditions dissociating only at pH of 2 or lower. Of the three pyrrolo(1,4)benzodiazepine antibiotics the reaction of anthramycin with DNA has been studied most thoroughly, chiefly by KOHN and coworkers31, 35,38). In a series of systematic studies, they have shown that the rate of reaction of anthramycin with DNA has the following characteristics.…”

mentioning

confidence: 99%