Date of Award

Fall 2025

Project Type

Dissertation

Program or Major

Chemistry

Degree Name

Doctor of Philosophy

First Advisor

Roy P Planalp

Second Advisor

Christine Caputo

Third Advisor

Anyin Li

Abstract

Metal chelators developed from peptides boast favorable attributes such as low toxicity, ease of synthesis, and high tunabilty to the target metal ion. It is for these reasons that peptides are used for metal sensing and sequestration in the body and environment. Herein, two unique sets of metal targeting peptides are discussed: (1) bifunctional Szeto-Schiller and Kelley peptide probes to signal the presence of and remove labile iron (Fe2+ and Fe3+) in the mitochondria, to mitigate the progression of Ferroptosis and (2) Pb2+ targeting peptides designed to exist in aqueous environments for the removal of toxic lead ions from waterways. These peptides were synthesized manually via solid phase peptide synthesis (SPPS) and determination of impurities and success of synthesis was carried out using analytical high-performance liquid chromatography (HPLC). Aspects of these peptides and their syntheses were explored, with special attention given to membrane lipophilicity, degree of epimerization due to synthetic protocols and protecting groups, and simulated metal complexation structures using computational modeling software. It was determined through these studies that the reagents used for peptide synthesis are heavily residue-dependent, and both the iron and lead (II) targeting peptides have shown promising metal chelation at early stages. Recommendations for further methods for analysis and determination of the lipophilicities of the iron probes are discussed, as well as additional computational studies and paths for sequence optimization for the lead (II) peptides.

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