Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/15989
Title: Development of new type of oligonucleotide as human topoisomerase I inhibitor
Authors: LI MING
Keywords: oligonucleotide, topoisomerase, anticancer, drug discovery,
Issue Date: 28-Sep-2008
Source: LI MING (2008-09-28). Development of new type of oligonucleotide as human topoisomerase I inhibitor. ScholarBank@NUS Repository.
Abstract: This dissertation describes two kinds of modified oligonucleotides, nick-containing dumbbell shaped oligonucleotide and Three-Way-Juntion oligonucletide, as efficient human topoisomerase I inhibitors. A series of nick-containing unimolecular oligonucleotids are developed as irreversible inhibitors of human topoisomerase I and their inhibitory effect on the relaxation reaction of negatively supercoiled DNA catalyzed by human topoisomerase I are examined. In addition, the correlation between the position of nick site and inhibitory effect, between the extremely stable hairpin loop and the inhibitory effect, as well as between the length of these nicked oliognucleotides and i are also discussed in this dissertation.A series of oligonucetides with Three-Way-Junction structures containing the topoisoerase I-binding sequences are also developed in this dissertation as efficient human topoisomerase I inhibitor by destroying the function of human topoisomerase I in relaxing supercoiled DNA in an irreversible way. Moreover, the results have also demonstrated that the inhibitory effect of structures with one lonely pair in one strand is much more efficient than that of the full matched counterparts.
URI: http://scholarbank.nus.edu.sg/handle/10635/15989
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