DNA binding properties of a new class of linked anthramycin analogs.
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.
Farmer
J D
JD
Department of Chemistry, Brown University, Providence, RI 02912.
Gustafson
G R
GR
Conti
A
A
Zimmt
M B
MB
Suggs
J W
JW
D000818:Animals; D000876:Anthramycin / Q000031:analogs & derivatives / Q000378:metabolism*; D001482:Base Composition; D002417:Cattle; D004247:DNA / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D012313:RNA / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013696:Temperature
D000876:Anthramycin; D012313:RNA; D004247:DNA