Preparation of a spermine conjugate of the bis-phenanthroline ligand Clip-Phen and evaluation of the corresponding copper complex.
We described the synthesis of conjugates of N, N-diethylethylenediamine and spermine with Clip-Phen, a new ligand with two 1,10-phenanthrolines linked by serinol. The ability of the copper complexes of these Clip-Phen conjugates to cleave PhiX174 DNA when activated by a reductant in the presence of air was compared to that of 1,10-phenanthroline copper complexes. The results indicated that Clip-Phen-spermine with copper was the most active DNA cleaver. Comparison with a conjugate having only one phenanthroline unit linked to spermine showed that the high activity of Clip-Phen-spermine-Cu was not only due to the presence of spermine, which increases the affinity of the Clip-Phen entity for the DNA, but was effectively due to the presence of the two bridged phenanthroline entities. The DNA cleavage activity of (Clip-Phen-spermine)CuCl2 was analyzed on a 167 bp restriction fragment and a 45-mer double-stranded oligonucleotide.
Pitié
M
M
Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse Cedex 4, France.
Meunier
B
B
D010584:Bacteriophage phi X 174 / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism*; D008024:Ligands; D015394:Molecular Structure; D009841:Oligonucleotides / Q000378:metabolism; D010618:Phenanthrolines / Q000737:chemistry* / Q000494:pharmacology; D013096:Spermine / Q000378:metabolism*
C115240:Clip-phen; D004279:DNA, Viral; D008024:Ligands; D009841:Oligonucleotides; D010618:Phenanthrolines; C038556:bis(1,10-phenanthroline)copper(1+) ion; D013096:Spermine; D003300:Copper; D004262:DNA Restriction Enzymes