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HIV-1 INTEGRASE AND HUMAN APE1: TWO DNA-PROCESSING
ENZYMES AND TWO DRUGGABLE TARGETS
by
Rasha Al Safi
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfilment of the
Requirements for the Degree
MASTER OF SCIENCE
(PHARMACEUTICAL SCIENCES)
May 2011
Copyright 2011 Rasha Al Safi
Object Description
| Title | HIV-1 integrase and human APE1: two DNA-processing enzymes and two druggable targets |
| Author | Al Safi, Rasha |
| Author email | rasha.alsafi@gmail.com; alsafi@usc.edu |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Pharmaceutical Sciences |
| School | School of Pharmacy |
| Date defended/completed | 2010-12-14 |
| Date submitted | 2011 |
| Restricted until | Unrestricted |
| Date published | 2011-01-31 |
| Advisor (committee chair) | Neamati, Nouri |
| Advisor (committee member) |
Duncan, Roger Okamoto, Curtis |
| Abstract | HIV-1 Integrase (IN) and the human apurinic/apyrimidinic endonuclease 1 (APE1) are two DNA-processing enzymes implicated in disease. IN catalyses the insertion of viral DNA into the host's chromatin, thereby marking the irreversible onset of infection. APE1 on the other hand, is involved in repairing the DNA damage induced by some classes of anticancer drugs, thus enabling the malignant cells to resist treatment and escape death. Given their role in disease, two in vitro assays were used to screen over a 1000 small molecules for potential inhibitory activity against IN and APE1. This undertaking culminated in the identification of novel structural scaffolds that can be used as platforms for the design of more potent inhibitors in the future. In another application, the in vitro activity of photoactivatable analogues of L-731,988, one of the earliest IN inhibitors, was assessed to validate their application as probes in future structural elucidation studies. |
| Keyword | HIV-1; integrase; APE1; cancer |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3632 |
| Rights | Al Safi, Rasha |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Safi-4142 |
| Archival file | uscthesesreloadpub_Volume29/etd-Safi-4142.pdf |
Description
| Title | Page 1 |
| Full text | HIV-1 INTEGRASE AND HUMAN APE1: TWO DNA-PROCESSING ENZYMES AND TWO DRUGGABLE TARGETS by Rasha Al Safi A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfilment of the Requirements for the Degree MASTER OF SCIENCE (PHARMACEUTICAL SCIENCES) May 2011 Copyright 2011 Rasha Al Safi |
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