Author ORCID Identifier
Semester
Fall
Date of Graduation
2025
Document Type
Dissertation
Degree Type
PhD
College
Eberly College of Arts and Sciences
Department
Chemistry
Committee Chair
Werner Geldenhuys
Committee Co-Chair
Hacer Karatas Bristow
Committee Member
Brian Popp
Committee Member
Fabien Goulay
Committee Member
Donald Adjeroh
Abstract
Reactive oxygen species play a crucial role in many cellular processes. Despite being a natural byproduct of cellular metabolism, overexpression of these species causes damage to the cell, leading to cell dysfunction. Central to the regulation of these highly reactive molecule is the mitochondria. Impairment in its function has been associated with oxidative stress within the cell. Herein, a ligand-based and structure-based approach to design new small molecules to inhibit mitochondrial redox proteins associated with oxidative stress and reactive oxygen species. In the first project two molecules were synthesized and characterized as potential monoamine oxidase B inhibitors. Results showed two promising molecules derived from the antidiabetic compound TT01001. In the second project, a small peptide derived from the protein-protein interaction between mitoNEET and BCL-2 is synthesized, and characterized through molecular dynamics simulation mitoNEET. Results showed that the peptide binds spontaneously to the key residues that coordinates the iron-cluster in mitoNEET. These two studies offer two simple approaches to effectively design drugs targeting oxidative stress related diseases.
Recommended Citation
Barbosa Belchior, Matheus, "Rational Design of Small Molecules Targeting Mitochondrial Redox Proteins" (2025). Graduate Theses, Dissertations, and Problem Reports. 13121.
https://researchrepository.wvu.edu/etd/13121
Included in
Computational Chemistry Commons, Medicinal and Pharmaceutical Chemistry Commons, Medicinal-Pharmaceutical Chemistry Commons, Pharmaceutics and Drug Design Commons, Physical Chemistry Commons