Date of Award
12-20-2024
Date Published
January 2023
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
Advisor(s)
Olga Makhlynets
Keywords
Hydrogels;Metalloproteins;Organophosphates;Peptides;Rheology;Self-healing
Subject Categories
Chemistry | Physical Sciences and Mathematics
Abstract
Peptide hydrogels are an important class of biomaterials that have gained significant attention in recent years. The stimuli responsive materials change their properties in response to pH, redox, temperature and enzymes and this property allowed us to design the materials with tunable properties based on their end application. This dissertation reports the de novo design, synthesis and characterization of short chain peptide sequences and optimizations of those in order to develop them into potential candidates in wound care and drug delivery applications. The investigation of these novel peptide sequences will open up new possibilities to tailor the properties through simple alterations in the backbone sequence. Chapter 1 of this dissertation presents a comprehensive review about peptide hydrogels including their synthesis techniques, antimicrobial properties, self-healing and flow behavior. This chapter further discusses about novel metallo proteins, their design and function. Chapter 2 describes our findings on two types of stimuli responsive (redox and pH) peptides that could be used in wound care applications. The developed hydrogels self-assemble through reversible non-covalent interactions and found to be self-healing. This chapter highlights the use of non-natural amino acids like pyridyl-alanine and azulenyl-alanine in peptide sequences and their role in metal coordination and improving antibacterial properties. The primary peptide sequence with pH responsive properties from chapter 2 was modified in order to develop a drug carrier to treat osteoarthritis and chapter 3 describes the findings from this work. The modification of C-term phenylalanine to methionine, helped to make the peptide responsive towards reactive oxygen species (ROS) while preserving its gel properties. The peptide was incorporated with insulin like growth factor (IGF-1) and its potential to release the encapsulated growth factor triggered by the joint fluid pH and ROS concentration was evaluated. Lastly chapter 4 provides insights on design of a novel biocatalyst using Due Ferri single chain (DFsc) protein which provides a binuclear site for metal ion incorporation and thus to tailor the hydrolytic activity of the catalyst. We investigated the effect of different metal combinations on the pNPP hydrolysis. Furthermore we carried out a computational analysis to elucidate the reaction mechanism of this enzyme and an EPR analysis to determine the structural and electronic characteristics of the designed catalyst. The content of this dissertation highlights the usability of short chain peptides as biomaterials and their ability to encapsulate drug molecules. These findings uncover a new platform for wound care and drug delivery applications but also paves the way for potential alternatives in future clinical applications.
Access
Open Access
Recommended Citation
Edirisinghe, Dona Imanga Upamadi, "Peptides and Metalloproteins: Evolution, Catalysis and Material Design" (2024). Dissertations - ALL. 2050.
https://surface.syr.edu/etd/2050