tailieunhanh - Báo cáo khóa học: Sequence selective binding of bis-daunorubicin WP631 to DNA

We have used footprinting techniques on a wide range of natural and synthetic footprinting substrates to examine the sequence-selective interaction of the bis-daunorubicin anti-biotic WP631 with DNA. The ligand produces clear DNase I footprints that are very different from those seen with other anthracycline antibiotics such as daunorubicin and nogalamycin. Footprints are found in a diverse range of sequences, many of which are rich inGT (AC) or GA (TC) residues. | Eur. J. Biochem. 271 3556-3566 2004 FEBS 2004 doi Sequence selective binding of bis-daunorubicin WP631 to DNA Keith R. Fox1 Richard Webster1 Robin J. Phelps1 Izabela Fokt2 and Waldemar Priebe2 1 School of Biological Sciences University of Southampton Bassett Crescent East Southampton UK 2The University of Texas MD Anderson Cancer Center Houston TX USA We have used footprinting techniques on a wide range of natural and synthetic footprinting substrates to examine the sequence-selective interaction of the bis-daunorubicin antibiotic WP631 with DNA. The ligand produces clear DNase I footprints that are very different from those seen with other anthracycline antibiotics such as daunorubicin and nogalamycin. Footprints are found in a diverse range of sequences many of which are rich in GT AC or GA TC residues. As expected the ligand binds well to the sequences CGTACG and CGATCG but clear footprints are also found at hexanucleotide sequences such GCATGC and GCTAGC. The various footprints do not contain any particular unique di- tri- or tetranucleotide sequences but are frequently contain the sequence G C A T A T G C . All sequences with this composition are protected by the ligand though it can also bind to some sites that differ from this consensus by one base pair. Keywords WP631 anthracycline antibiotic daunorubicin footprinting sequence recognition. A large number of ligands are known to bind to DNA and several of these are important therapeutic agents particularly in the treatment of cancer. However most such agents have little or no sequence selectivity and are therefore extremely cytotoxic and affect all rapidly dividing cells. One goal for cancer chemotherapy is therefore to produce compounds that only interact with specific genes or gene products. The deciphering of many complete genomes gives new impetus to the search for molecules that interfere with the activity of individual genes. Examples of strategies aimed at realizing .