Chemical and Biomolecular Engineering - Theses

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    Diversification of peptide architectures by surface-initiated ring-opening polymerization
    Harris Wibowo, Steven ( 2015)
    This thesis reports the successful utilisation of surface-initiated ring opening polymerization (SI-ROP) as a versatile technique for the formation of peptide-based materials with tunable secondary conformation, architecture and applications. Chapter 1 provides an overview of the various methodologies for the synthesis and preparation of polypeptides as well as the fabrication techniques employed to create peptide-based advanced functional materials for various applications. This chapter also highlights the current synthetic limitations and challenges facing the field, and set the scene for the studies presented in this thesis. In Chapter 2, we introduced a novel approach to form cross-linked poly(L-glutamic acid) (PLGA) free-standing films (i.e., capsules) by synergistically leveraging the use of SI-ROP, hyperbranched macroinitiator, and cross-chain termination reaction to. In this assembly approach, during the SI-ROP of BLG-NCA from amine-functionalised silica particles, the propagating amine groups undergo nucleophilic attack at the carbonyl carbon of the benzyl-ester side-groups on adjacent polymer chains (i.e., cross-chain termination reactions). This event led to the formation of inactive amide groups which consequently cross-link the grafted peptide chains. Following the deprotection of remaining benzyl protecting groups and dissolution of the silica template (via hydrofluoric acid treatment), the cross-linked peptide chains formed free-standing architectures in the form of thin polypeptide capsules. While cross-chain termination was verified by conducting Maldi-Tof analysis and chain extension studies, the extensive covalent crosslinking results in stability of PLGA-capsules at various pH conditions and in the presence of H-bond breaker urea. The thickness of the capsules could be tuned by variation of the polymerization time and initial monomer concentration. Meanwhile, the composition and functionality could be tuned by using a combination of different amino acid NCA derivatives. Furthermore, despite the highly cross-linked structure, the capsules were found to be biodegradable in the presence of proteolytic enzymes. Not only did this study present a novel cross-linking approach, the results also open exciting opportunities for the development of biomedical (nano)devices with excellent mechanical stability, degradability and tunable functionality. In Chapter 3, we took advantage of SI-ROP of β-sheet forming α-amino acid N-carboxyanhydrides to form grafted polypeptides which self-assemble into β-sheet in situ. Here, we demonstrate SI-ROP as a simple, rapid, and robust strategy to form novel polypeptide β-sheet architectures with tailored shapes and dimensions that is yet to be reported in the literature. As the peptide-grafts remain anchored during SI-ROP, the formation of β-sheet-forming peptide grafts are controlled in a spatial and temporal fashion which help avoid the unconstrained random aggregation of β-sheet polypeptides formed in solution. The study reveals that after a certain SI-ROP time, H-bonding between the surface-anchored peptide grafts results in β-sheet architectures assembled in situ that possess a rigid and porous structured surface. Since both the polypeptide formation and self-assembly into β-sheet structures are surface-driven, the resulting H-bonded peptide grafts adopt the 3D shape of the template. Following template dissolution, stable and well-defined free-standing polypeptide shell architectures were formed. In this study, we found that SI-ROP time and initial NCA monomer concentration influences the morphology of the poly(L-valine) (PVal) shells. Notably, these shells are stabilised by both hydrophobic interaction and H-bonding which results in their stability under various pH conditions, high temperature and in the presence of denaturants such as urea and guanidine hydrochloride. Nevertheless, we found that the architectures are still enzyme degradable and chemical functionalities can be introduced via chain extension reaction. In the second part of the thesis (Chapter 4), we presented the diverse applications of peptide-based materials prepared by SI-ROP of NCA derivatives. First, peptide nano-coatings with tailored surface wetting properties were formed on a range of organic (cellulose and cotton) and inorganic (glass) substrates via SI-ROP of judiciously-selected amino acid NCA derivatives. In this study, the film thickness, surface roughness and wettability were tuned by controlling the polymerization time and the type of NCA derivative used (i.e., lysine or valine). While poly(L-lysine) coatings are hydrophilic, poly(L-valine) coatings exhibit water-repellent properties. The functional polypeptide nano-coatings can potentially be applied to waterproof woven fabrics, macromolecular separation technologies, biodiagnostic sensors and sustained drug-release wound dressings. Following this study, we report the unique capacity of the free-standing PVal-shells reported in Chapter 3 for the non-covalent entrapment and conjugation of various materials ranging from metal nanoparticles, to quantum dots, synthetic polymers, drug molecules and protein. Preparation of metal nanoparticles-peptide hybrid materials demonstrate potential applications in organic catalysis and diagnostic devices while entrapment of quantum dots, polymers, proteins and drug molecules open up opportunities for the convenient fabrication of biodiagnostic and drug-delivery vehicles. Finally, to further expand the diversity of peptide-based architectures we proposed future fundamental and fabrication studies that leverages the collective knowledge gained by conducting studies reported in this thesis (Chapter 5).