Targeting latent HIV : the design, synthesis and evaluation of prostratin analogs

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Abstract/Contents

Abstract
The theme of this work is to utilize hypothesis driven synthetic manipulation to enhance our understanding of the biological effects of prostratin and its highly potent analogs, and to utilize this understanding for the improvement of the therapeutic properties thereof. Prostratin, a natural product activator of protein kinase C (PKC), is a molecule of interest for targeting latent HIV, the primary obstacle to HIV eradication in infected individuals on effective highly active antiretroviral therapy. Chapter one describes the current state of the HIV pandemic, therapeutic strategies, prospects for a cure, and clinical studies toward immune activation therapy. Chapter two is a seminal and complete analysis of the biological effects of prostratin, a natural product candidate for immune activation therapy. Chapter three presents the design, synthesis, and evaluation of highly potent analogs of prostratin via an efficient semi-synthetic route. Chapter four presents the design and synthesis of isotopically labeled prostratin analogs to be utilized in solid-state NMR studies probing the active conformation of the PKC/activator complex in its membrane associated state. Chapter five presents the design, synthesis, and evaluation of prodrugs of prostratin and prostratin analogs for the optimization of pharmacologic properties.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2012
Issuance monographic
Language English

Creators/Contributors

Associated with Beans, Elizabeth Josephine
Associated with Stanford University, Department of Chemistry
Primary advisor Wender, Paul A
Thesis advisor Wender, Paul A
Thesis advisor Huestis, Wray
Thesis advisor Kool, Eric T
Advisor Huestis, Wray
Advisor Kool, Eric T

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Elizabeth Josephine Beans.
Note Submitted to the Department of Chemistry.
Thesis Thesis (Ph.D.)--Stanford University, 2012.
Location electronic resource

Access conditions

Copyright
© 2012 by Elizabeth Josephine Beans
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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