Mechanism of action studies on the FR-9000482 class of antitumor antibiotics
| dc.contributor.author | Rajski, Scott Raymond, author | |
| dc.contributor.author | Williams, Robert M., advisor | |
| dc.date.accessioned | 2022-11-28T17:44:49Z | |
| dc.date.available | 2022-11-28T17:44:49Z | |
| dc.date.issued | 1997 | |
| dc.description.abstract | The interactions of members of the FR-900482 class of antitumor antibiotic agents with DNA has been examined. Importantly, the first in vitro demonstration of nucleic acid interstrand cross-linking has been reported and the DNA base pair sequence specificity of the cross-linking event has been elucidated. These agents demonstrate a high degree of selectivity for 5'-CG-3' sequences of DNA. As such, bio-mechanistic analogy between these compounds and the clinically employed compound Mitomycin Chas been shown. Efforts have also examined extensively the ability of these agents to give rise to orientation isomers of each respective cross-link and their different properties. DNA-protein cross-linking by these agents has also been examined. A sequence-specific DNA-peptide binding motif has been identified which undergoes drug-mediated DNA-protein cross-linking. This is the first reported instance of a mitosene based-minor groove DNA-protein cross-link event. Significantly, the motif examined is characteristic of tissues which bear striking similarity to those of cancerous cell lines. | |
| dc.format.medium | doctoral dissertations | |
| dc.identifier.uri | https://hdl.handle.net/10217/235834 | |
| dc.language | English | |
| dc.language.iso | eng | |
| dc.publisher | Colorado State University. Libraries | |
| dc.relation | Catalog record number (MMS ID): 991008176079703361 | |
| dc.relation | RC271.A65R35 1997 | |
| dc.relation.ispartof | 1980-1999 | |
| dc.rights | Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright. | |
| dc.subject | Antineoplastic antibiotics | |
| dc.subject | DNA-drug interactions | |
| dc.title | Mechanism of action studies on the FR-9000482 class of antitumor antibiotics | |
| dc.type | Text | |
| dcterms.rights.dpla | This Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). | |
| thesis.degree.discipline | Chemistry | |
| thesis.degree.grantor | Colorado State University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |
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