MEDI 307 |
| As a specific enzyme releasing the topological stress of DNA generated by several cellular press such as replication and transcription, human topoisomerase I has been known to be a molecular target of various anticancer agents, such as the camptothecins, indolocarbazoles and indenoisoquinolines. Moreover, it has also been shown in the past few years that apart from the supercoiled structures, a few linear duplex oligonucleotides can act as substrate of eukaryotic topoisomerase I in vitro as well. Subsequent investigation in this research field demonstrated to a further step that when a nick was present in the topoisomerase I-binding sequence near its cutting sites, one strand of duplex oligonucleotide substrates could generate covalent linkage with the enzyme in an irreversible manner. Inspired by the previous discoveries, we herein developed a series of nick-containing unimolecular oligonucleotides as irreversible inhibitors of human topoisomerase I and examined their inhibitory effect on the relaxation reaction of negatively supercoiled DNA catalyzed by human topoisomerase I. The correlation between the position of nick site and inhibitory effect as well as between the length of these nicked oligonucleotides and IC50 values will be discussed during our poster presentation.
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Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Medicinal Chemistry |
