Effects of variation in the structure of spermine on the association with DNA and the induction of DNA conformational changes.
The effects of spermine and spermine analogues on the B-Z transition of poly(dG-me5dC) and on the aggregation and 'melting' temperature of calf thymus DNA were studied by spectroscopic methods. The association constants of these polyamines with double- and single-stranded calf thymus DNA were calculated from their effects on the melting temperature. The effect of these compounds on the release of ethidium bromide (EB) from an EB-DNA complex were measured by a spectrofluorimetric method. This efficiency of the polyamine-induced B-Z transition strongly depended on the length of the central carbon chains of the compounds and on the functional groups attached to the carbon chains. Both the terminal primary amino groups and the length of the central carbon chain affected the aggregation of DNA. The affinity of the analogues for DNA increased as the number of n-butyl groups increased, but decreased with either an increase or a decrease in the length of the central carbon chain. The effect of spermine and spermine analogues on the release of EB from an EB-DNA complex did not always correlate with the affinities of analogues for calf thymus DNA. In particular, tetra-amines with more than one n-butyl group bound better to DNA than did spermine, but released bound EB and induced aggregation of DNA less well than did spermine. We postulate that either a bend and/or other localized conformational changes of DNA are responsible for the spermine-induced aggregation of DNA and the release of EB from the EB-DNA complex.
Basu
H S
HS
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143.
Schwietert
H C
HC
Feuerstein
B G
BG
Marton
L J
LJ
D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000187:drug effects / Q000378:metabolism; D004996:Ethidium / Q000378:metabolism; D006358:Hot Temperature; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D013056:Spectrophotometry, Ultraviolet; D013096:Spermine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004277:DNA, Single-Stranded; D013096:Spermine; D004247:DNA; D004996:Ethidium