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Structural and functional studies of cysteine-rich proteomimetic scaffolds

Rao, Shilpa Ravindra (2024) Structural and functional studies of cysteine-rich proteomimetic scaffolds. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Linear chains of covalently connected amino acids direct the proteins to fold into specific three-dimensional shapes and thereby control the function of proteins. Altering the backbone connectivity in natural proteins by blending natural with artificial building blocks is a powerful approach to generate proteomimetic scaffolds. Though significant advancements have been made in the field of proteomimetics, a generalizable set of design principles for developing such artificial molecules still remain elusive. A main focus of this dissertation is understanding the structural and functional consequences of modifying the backbone composition in cysteine-rich proteomimetic scaffolds. Chapter 2 of this dissertation sheds light on modifying metal-binding β-turns found in zinc finger domains without compromising folded structure or stability. In chapters 4 and 5, we describe our rational approach to develop structural and functional mimics of a multidomain zinc finger protein and a disulfide-rich antimicrobial peptide. Additionally, in chapter 3, we document our efforts to advance the use of proton chemical shift information obtained by NMR methods to understand folding behavior in protein-like artificial backbones. Collectively, the body of work presented in this dissertation aims to provide more insights into the impacts of backbone modifications on folded structure and function of proteomimetic scaffolds.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Rao, Shilpa Ravindrashr64@pitt.edushr64
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberChilders, William Sethwschild@pitt.edu
Committee MemberLiu, Pengpengliu@pitt.edu
Committee MemberIshima, Riekoishima@pitt.edu
Thesis AdvisorHorne, William Sethhorne@pitt.edu
Date: 10 January 2024
Date Type: Publication
Defense Date: 20 June 2023
Approval Date: 10 January 2024
Submission Date: 8 December 2023
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 194
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: Proteomimetics, backbone modifications, zinc fingers, cysteine rich scaffolds
Date Deposited: 10 Jan 2024 14:00
Last Modified: 10 Jan 2024 14:00
URI: http://d-scholarship.pitt.edu/id/eprint/45633

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