Amplification of bleomycin-mediated degradation of DNA by polyamines.
The degradation of calf thymus DNA by a ferrous complex of bleomycin A2 or Blenoxane (a mixture consisting mainly of BLM-A2 and BLM-B2) is enhanced by polyamines higher than ethylenediamine. The QSAR analysis gave excellent correlation between the experimental amplification results and calculated valence molecular connectivity indices of the third order and path type for the protonated polyamines. A new amplifier of bleomycin activity has been synthesized and its interaction with DNA has been studied. This compound contains a DNA-intercalating moiety and a polyamine portion, two independent amplification systems in the same molecule. The role of the C-terminus of bleomycin as the intramolecular amplifier for the degradation of DNA is discussed.
Strekowski
L
L
Department of Chemistry, Georgia State University, Atlanta 30303.
Mokrosz
M
M
Mokrosz
J L
JL
Strekowska
A
A
Allison
S A
SA
Wilson
W D
WD
D000818:Animals; D001761:Bleomycin / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D004247:DNA / Q000378:metabolism*; D004357:Drug Synergism; D009682:Magnetic Resonance Spectroscopy; D011073:Polyamines / Q000138:chemical synthesis / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000494:pharmacology; D014783:Viscosity
D011073:Polyamines; D011743:Pyrimidines; D013876:Thiophenes; D001761:Bleomycin; C050499:N-(2''-(dimethylamino)ethyl)-4-(thien-2'-yl)pyrimidin-2-amine; D004247:DNA