Abstract
Since its discovery in the 1960s, pacilitaxel (PTX) has
been one of the most important discoveries in the field of cancer
therapeutics, and is currently used in the treatment of metastatic
breast cancer, ovarian carcinoma, and AIDS-related Kaposi-Sarcoma.
PTX works by binding to the β-tubulin subunit of
cellular microtubules, and this PTX-tubulin complex stabilizes the
microtubule structure preventing cells from completing mitotic
division. In an effort to synthesize more targeted analogs of PTX,
researchers have been trying to determine the conformation PTX
assumes upon binding the β-tubulin subunit. In
recent years, there have been two major conformations suggested.
The first is the T-Taxol conformation suggested by James P. Snyder
of Emory University and the second is the REDOR-Taxol conformation
suggested by Iwao Ojima of Stony Brook University. Because these
two conformations contain many similarities, it is difficult to
determine which is the correct conformation. It is therefore the
purpose of this research to synthesize a constrained PTX analog
that has the potential to shed light on this topic.
Table of Contents
List of Figures
List of Schemes
List of Abbreviations
I. Introduction
Taxol: A History and Introduction...1
Microtubules: Background and Interactions with Taxol...4
Conformationally Constrained Taxol...6
II. Results and Discussion
Results and Discussion...8
Conclusion...11
Future Plans...12
III. Experimental
Experimental Methods...12
Experimental...13
References...20
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