DNA binding properties of a new class of linked anthramycin analogs.

AUTOR(ES)

Farmer, J D

RESUMO

We have investigated the DNA binding properties of the anthramycin analogues 4, 5, and 6 using fluorescence spectroscopy. A considerable fluorescence enhancement occurs when pyrrolo [1,4] benzodiazepines (P[1,4]Bs) are covalently attached to duplex DNA, which was used to show that neither the presence of RNA, single-stranded DNA, or protein had any effect on the degree of fluorescence enhancement resulting from the incubation of 5 and 6 with DNA. The enhancement was found to be dependent on the presence of the imine functionality in each of the compounds. A wavelength of 320 nm was used to excite the chromophore and its emission wavelength maximum was 420 nm. Additionally, we have discovered that the P[1,4]B ring system exhibits exceptionally favorable fluorescence polarization anisotropy (FPA) decay characteristics. For these more detailed fluorescence measurements, we used the structurally simpler analogue 4,. The time resolved maximum FPA for 4 in glycerol at 25 degrees C is 0.28. This result indicates that the P[1,4]B family of antibiotics could serve as sensitive probes of DNA dynamics in the 0.1 to 35 ns time scale.

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