Curved oligonucleotide constructs as human topoisomerase I inhibitors : a mechanistic study of the enzyme’s recognizing passway.
Topoisomerases I are enzymes that alter the topological states of DNA. In eukaryotic organisms, including human being, Topoisomerase I is diverse and significant. It is discovered that there are more than normal amount of Topo I enzymes in the tumour cells, making it a potential drug target for canc...
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| Format: | Final Year Project (FYP) |
| Language: | English |
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2010
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| Online Access: | http://hdl.handle.net/10356/38601 |
| _version_ | 1826130444501909504 |
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| author | Zhao, Guanjia. |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Zhao, Guanjia. |
| author_sort | Zhao, Guanjia. |
| collection | NTU |
| description | Topoisomerases I are enzymes that alter the topological states of DNA. In eukaryotic organisms, including human being, Topoisomerase I is diverse and significant. It is discovered that there are more than normal amount of Topo I enzymes in the tumour cells, making it a potential drug target for cancer therapy. The traditional Topo I inhibitors are organic molecules, and this report aims to develope short oligonucleotides as possible Topo I inhibitors, and also to study the recognition mechanism of human Topoisomerase I with the substrate DNA molecules. In this project, it was not only evidenced that DNA curvature indeed was crucial for the enzyme-substrate recognition, but also the minimum number of A-tracts in the curved constructs was determined. What’s more, inhibitory effects of different types of curvature on Topo I were compared to show that a two-way-curved oligonucleotide was more effective to inhibit Topo I activity than the corresponding one-way-curved oligonucleotide, and this finding might be helpful for better understanding of the enzyme-DNA recognition mechanism. |
| first_indexed | 2024-10-01T07:56:35Z |
| format | Final Year Project (FYP) |
| id | ntu-10356/38601 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:56:35Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | ntu-10356/386012023-02-28T23:18:15Z Curved oligonucleotide constructs as human topoisomerase I inhibitors : a mechanistic study of the enzyme’s recognizing passway. Zhao, Guanjia. School of Physical and Mathematical Sciences Li Tianhu DRNTU::Science::Biological sciences::Biochemistry Topoisomerases I are enzymes that alter the topological states of DNA. In eukaryotic organisms, including human being, Topoisomerase I is diverse and significant. It is discovered that there are more than normal amount of Topo I enzymes in the tumour cells, making it a potential drug target for cancer therapy. The traditional Topo I inhibitors are organic molecules, and this report aims to develope short oligonucleotides as possible Topo I inhibitors, and also to study the recognition mechanism of human Topoisomerase I with the substrate DNA molecules. In this project, it was not only evidenced that DNA curvature indeed was crucial for the enzyme-substrate recognition, but also the minimum number of A-tracts in the curved constructs was determined. What’s more, inhibitory effects of different types of curvature on Topo I were compared to show that a two-way-curved oligonucleotide was more effective to inhibit Topo I activity than the corresponding one-way-curved oligonucleotide, and this finding might be helpful for better understanding of the enzyme-DNA recognition mechanism. Bachelor of Science in Chemistry and Biological Chemistry 2010-05-13T01:18:49Z 2010-05-13T01:18:49Z 2010 2010 Final Year Project (FYP) http://hdl.handle.net/10356/38601 en 34 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences::Biochemistry Zhao, Guanjia. Curved oligonucleotide constructs as human topoisomerase I inhibitors : a mechanistic study of the enzyme’s recognizing passway. |
| title | Curved oligonucleotide constructs as human topoisomerase I inhibitors : a mechanistic study of the enzyme’s recognizing passway. |
| title_full | Curved oligonucleotide constructs as human topoisomerase I inhibitors : a mechanistic study of the enzyme’s recognizing passway. |
| title_fullStr | Curved oligonucleotide constructs as human topoisomerase I inhibitors : a mechanistic study of the enzyme’s recognizing passway. |
| title_full_unstemmed | Curved oligonucleotide constructs as human topoisomerase I inhibitors : a mechanistic study of the enzyme’s recognizing passway. |
| title_short | Curved oligonucleotide constructs as human topoisomerase I inhibitors : a mechanistic study of the enzyme’s recognizing passway. |
| title_sort | curved oligonucleotide constructs as human topoisomerase i inhibitors a mechanistic study of the enzyme s recognizing passway |
| topic | DRNTU::Science::Biological sciences::Biochemistry |
| url | http://hdl.handle.net/10356/38601 |
| work_keys_str_mv | AT zhaoguanjia curvedoligonucleotideconstructsashumantopoisomeraseiinhibitorsamechanisticstudyoftheenzymesrecognizingpassway |