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Chemical Probes for Biological Discovery

Emanuelson, Cole (2024) Chemical Probes for Biological Discovery. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Chemical probes are important tools in the chemical biologist’s repertoire for investigating the mechanisms of biological processes. Probes ranging in size from small molecules to functional proteins are instrumental to the study of complex biological pathways that constitute living organisms. Additionally, properly validated chemical probes can serve as proof-of-concept for the development of drug-like molecules that can translate to therapies for patients. Here, I describe my contributions to the discovery and characterization of a diverse array chemical probes including: (1) DNA-based devices for molecular computing, (2) small molecule probes for the inhibition of miRNA and (3) peptide-based probes for the study protein structure and protein-protein interactions.
The ensuing chapters are grouped into three sections with the central focus of each section representing one fragment of the central dogma of molecular biology. The first section details the development of DNA-based devices that utilize photo-caged nucleobases and templated chemical synthesis are described. These devices take the form of DNA strand displacement cascades designed to mimic the operation of Boolean logic gates. Next, RNA targeted probes are discussed, with specific attention given to the development of small molecule inhibitors of microRNA-122 and related probe discovery efforts. Finally, a discussion of the design of synthetic peptides aimed towards studying protein function and the control of protein-protein interactions.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Emanuelson, Coleemanuelsonc@gmail.comemanuelsonc@pitt.edu0000-0001-6903-6958
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDeiters, Alexanderdeiters@pitt.edu
Committee MemberArmitage, Brucearmy@cmu.edu
Committee MemberChilders, Sethwschild@pitt.edu
Committee MemberWeber, Stephensweber@pitt.edu
Date: 8 May 2024
Date Type: Publication
Defense Date: 6 September 2022
Approval Date: 8 May 2024
Submission Date: 8 September 2022
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 233
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: DNA, Templated Chemistry, microRNA, Photo-activation
Date Deposited: 08 May 2025 12:20
Last Modified: 08 May 2025 12:20
URI: http://d-scholarship.pitt.edu/id/eprint/45938

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