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Development of Protein-Catalyzed Capture (PCC) Agents with Application to the Specific Targeting of the E17K Point Mutation of AKt1

Citation

Deyle, Kaycie Marie (2014) Development of Protein-Catalyzed Capture (PCC) Agents with Application to the Specific Targeting of the E17K Point Mutation of AKt1. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/F8HW-TX51. http://resolver.caltech.edu/CaltechTHESIS:05272014-114201666

Abstract

This thesis describes the expansion and improvement of the iterative in situ click chemistry OBOC peptide library screening technology. Previous work provided a proof-of-concept demonstration that this technique was advantageous for the production of protein-catalyzed capture (PCC) agents that could be used as drop-in replacements for antibodies in a variety of applications. Chapter 2 describes the technology development that was undertaken to optimize this screening process and make it readily available for a wide variety of targets. This optimization is what has allowed for the explosive growth of the PCC agent project over the past few years.

These technology improvements were applied to the discovery of PCC agents specific for single amino acid point mutations in proteins, which have many applications in cancer detection and treatment. Chapter 3 describes the use of a general all-chemical epitope-targeting strategy that can focus PCC agent development directly to a site of interest on a protein surface. This technique utilizes a chemically-synthesized chunk of the protein, called an epitope, substituted with a click handle in combination with the OBOC in situ click chemistry libraries in order to focus ligand development at a site of interest. Specifically, Chapter 3 discusses the use of this technique in developing a PCC agent specific for the E17K mutation of Akt1. Chapter 4 details the expansion of this ligand into a mutation-specific inhibitor, with applications in therapeutics.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:PCC Agent, OBOC Screening, Click Chemistry
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Awards:Everhart Distinguished Graduate Student Lecture Series, 2014.
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Heath, James R.
Thesis Committee:
  • Rees, Douglas C. (chair)
  • Dougherty, Dennis A.
  • Bercaw, John E.
  • Heath, James R.
Defense Date:19 May 2014
Record Number:CaltechTHESIS:05272014-114201666
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:05272014-114201666
DOI:10.7907/F8HW-TX51
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8398
Collection:CaltechTHESIS
Deposited By: Kaycie Butler Deyle
Deposited On:30 May 2014 20:28
Last Modified:11 Apr 2019 17:49

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