Search for new types of deoxyribozymes and development of human topoisomerases inhibitors on the basis of oligonucleotides

Abstract

The focuses of our discussion in the first part of this thesis are on the search and confirmation of new types of deoxyribozymes that possess DNA self-cleaving activity. Certain guanine-rich oligonucleotides with potential to form G-quadruplexes were constructed and their self-cleaving activities are examined during our investigations. Our studies demonstrated that certain guanine-rich sequences could exhibit highly site-specific self-cleaving activities. Subsequent studies on the basis of polyacrylamide gel electrophoresis and Mass Spectrometry confirmed that this self-cleavage reaction proceeds indeed with hydrolysis pathway.The emphases of our studies in the second part of this thesis are on the search and development of human topoisomerase I/II inhibitors on the basis of oligonucleotides. Certain non-supercoiled DNA sequences with DNA imperfections such as gap or mismatch next to the topoisomerases cleavage site are designed. Our studies demonstrated some of our newly designed oligonucleotides could inhibit human topoisomerases with high efficiency. The highly efficient inhibition could be caused by the covalent bond linkage between our newly designed oligonucleotides and human topoisomerases when they are allowed to interact with each other.