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Bioorthogonal and Photoswitchable Tools for Protein Control

Shade, Olivia Hanson (2024) Bioorthogonal and Photoswitchable Tools for Protein Control. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

I have utilized key tools in chemical biology research, namely bioorthogonal chemistry, genetic code expansion, and targeted protein degradation to investigate new ways to impart specific and selective control over protein function. I have developed and optimized a new tool for in cellulo protein bioconjugation quantification using simple western blotting techniques (Chapter 1.0) and site-specifically recruited bioorthogonally modified E3 ligase ligands to proteins with an expanded genetic code for investigation of protein degradability (Chapter 2.0). Expanding on these methods, I have also imparted optical control of site-specific degradation via photocaged, bioorthogonal E3 ligase ligands (Chapter 3.0) and developed a tool for the investigation of hydrophobic degradation through bioconjugation of two hydrophobic ligands (Chapter 4.0).
In addition to my extensive work in conjugating various ligands to proteins with expanded genetic codes and investigating the resultant impact on protein expression, I have also utilized photoswitchable molecules to impart reversible optical control over proteins and peptides. We developed the best photoswitchable amino acid to date and utilized it to impart optical control over protein translation (Chapter 6.0). I have also developed a series of fluorinated azobenzene chromophores for rigid stapling and reversible isomerization of strategically designed peptides (Chapter 7.0), and fluorinated unnatural amino acids for photocontrol over protein structure and resultant function in biological systems (Chapter 8.0).

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Shade, Olivia Hansonohs1@pitt.eduohs1
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDeiters, Alexanderdeiters@pitt.edudeiters
Committee MemberChilders, W. Sethwschild@pitt.eduwschild
Committee MemberHorne, W. Sethhorne@pitt.eduhorne
Committee MemberKhare, Sagarkhare@chem.rutgers.edu
Date: 20 December 2024
Date Type: Publication
Defense Date: 15 November 2024
Approval Date: 20 December 2024
Submission Date: 1 December 2024
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 340
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: bioorthogonal, unnatural amino acid, targeted protein degradation, photoswitch, azobenzene, E3 ligase ligand, photocage, optical control
Date Deposited: 20 Dec 2024 14:39
Last Modified: 20 Dec 2024 14:39
URI: http://d-scholarship.pitt.edu/id/eprint/47151

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