INTERMOLECULAR CROSS-LINKING OF DNA THROUGH BIFUNCTIONAL INTERCALATION OF AN ANTI-TUMOR ANTIBIOTIC, LUZOPEPTIN-A (BBM-928A)

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (6) , 2718-2724
Abstract
A bifunctional intercalator may intercalate with DNA in at least 2 ways. Both intercalating moieties may intercalate with the same DNA molecule (type I, intramolecular cross-linking) or with 2 separate DNA molecules (type II, intermolecular cross-linking). Production of type I is often assumed. Type II biintercalation was suggested, but no direct evidence was reported. Endonuclease-restricted PM2 phase or pBR322 plasmid DNA fragments were treated with the bifunctional intercalative antitumor antibiotics, luzopeptin A (BBM-928A) and echinomycin, and analyzed by agarose gel electrophoresis. Luzopeptin A treatment produced additional DNA bands which were the products of type II biintercalation. The types of restriction fragments involved were identified. Maximal type II biintercalation occurred at a luzopeptin A/DNA range of 0.14-0.18, at which > 50% of the total DNA molecules were involved. Type II products were converted gradually to type I products upon prolonged incubation at 37.degree., probabably due to the tendency for intermolecular bonds to disrupt. Echinomycin treatment failed to produce type II products, probably because of a DNA-binding affinity weaker than that of luzopeptin A. It is possible to use the present gel system to demonstrate the type II biintercalation for strong biintercalators, but milder systems are needed for weak biintercalators.

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