Drug binding by branched DNA: selective interaction of tetrapyridyl porphyrins with an immobile junction.
The differential binding of a number of water-soluble cationic porphyrins to a branched DNA molecule is reported. Tetrakis(4-N-methylpyridiniumyl)porphine (H2TMpyP-4) interacts near the branch point with an immobile DNA junction formed from four 16-mer strands. Its Cu(II) and Ni(II) derivatives show stronger preferential binding in the neighborhood of the branch point. Axially liganded derivatives, Zn, Co, and Mn, also interact near this branch point, but in a different way. We use the reagents methidiumpropyl-EDTA.Fe(II) [MPE.Fe(II)] and bis(o-phenanthroline)copper(I) [(OP)2Cu(I)] to cleave complexes of DNA duplex controls and the junction with these porphyrins. The resulting cleavage patterns are consistent with previous evidence that the branch point provides a strong site for intercalative binding agents, which is not available in unbranched duplexes of identical sequence. The preferential scission by (OP)2Cu(I) in the presence of Ni and Cu porphyrins near the branch point exceeds that seen for any agents we have studied. This hyperreactivity is not seen in the case of porphyrins with axial ligands, ZnTMpyP-4, CoTMpyP-4, and MnTMpyP-4, although these also interact near the branch point. The Zn derivative tends to protect sites close to the branch point from cutting, while the Co and Mn porphyrins moderately enhance cleavage of sites in this region.
Lu
M
M
Department of Chemistry, New York University, New York 10003.
Guo
Q
Q
Pasternack
R F
RF
Wink
D J
DJ
Seeman
N C
NC
Kallenbach
N R
NR
D001483:Base Sequence; D003035:Cobalt / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D003720:Densitometry; D008024:Ligands; D008345:Manganese; D008652:Mesoporphyrins / Q000378:metabolism; D008969:Molecular Sequence Data; D009532:Nickel / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
D008024:Ligands; D008652:Mesoporphyrins; D011166:Porphyrins; C021096:tetra(4-N-methylpyridyl)porphine; D003035:Cobalt; D008345:Manganese; D003300:Copper; D009532:Nickel; D004247:DNA; D015032:Zinc