Document Type
Thesis
Date of Award
10-31-1993
Degree Name
Master of Science in Biomedical Engineering - (M.S.)
Department
Biomedical Engineering Committee
First Advisor
David S. Kristol
Second Advisor
Janardan Yadav
Third Advisor
Mukund J. Modak
Abstract
An active analog approach to receptor mapping was used to identify the three dimensional structural characteristics associated with a series of thymidine nucleoside analog inhibitors of HIV-1 reverse transcriptase (RT) that may be essential for their activity. Atomic substitutions at the 5 and 3' positions of nucleoside analogs confer global structural and electrostatic changes that result in either increased or diminished inhibitory activity. From a structural perspective, the activity differences can be attributed to the presentation of select atoms in three dimensional motifs that are common to all active compounds and absent or distorted in inactive/poorly active compounds.
The identification of these characteristics will complement more direct studies of the RT structure by providing a specific three dimensional orientation for substrate and inhibitor molecules at their receptor site. They can also serve as a three dimensional template for the screening of potentially active compounds; thus, aiding in the development and identification of new, more potent and selective inhibitor molecules. The characteristics identified are common to 15 thymidine nucleoside analog inhibitors of RT and have allowed the inference of a three dimensional map of the HIV-1 RT receptor site.
Recommended Citation
Fisher, Mark A., "Computer assisted molecular modeling of thymidine nucleoside analog inhibitors of HIV-1 reverse transcriptase" (1993). Theses. 1753.
https://digitalcommons.njit.edu/theses/1753
