Design of Multidomain Peptides and Collagen Mimetic Peptides for Biological Applications
| dc.contributor.advisor | Hartgerink, Jeffrey D. | en_US |
| dc.creator | Li, I-Che | en_US |
| dc.date.accessioned | 2019-05-17T14:48:48Z | en_US |
| dc.date.available | 2019-05-17T14:48:48Z | en_US |
| dc.date.created | 2018-05 | en_US |
| dc.date.issued | 2018-04-05 | en_US |
| dc.date.submitted | May 2018 | en_US |
| dc.date.updated | 2019-05-17T14:48:48Z | en_US |
| dc.description.abstract | Supramolecular chemistry plays an important role in designing self-assembling peptides. The goal of this work is to design, synthesize, and customize multidomain peptides (MDPs) and collagen mimetic peptides (CMPs) for biological applications. In the first part of this work, we modify the MDP nanofibers to achieve controlled drug release and macroscopic anisotropy. In the second part, we explored residue substitutions in CMPs to capture helical conformations and to target natural collagens. As a type of peptide hydrogel, MDPs respond to external shearing forces and have reversible self-assembly under mild conditions. Controlled drug release is accomplished by modifying the hydrophobic interior of the MDP to construct hollow fibers for the encapsulation of anti-cancer drugs, antibiotics, or nonsteroidal anti-inflammatory drugs. Macroscopic anisotropy was achieved by modifying the hydrophilic exterior of the MDP to achieve organized self-assembly into parallel aligned fiber bundles. With the help of shearing forces of syringe extrusion and the incorporation of the amino acid DOPA (3,4-dihydroxyphenylalanine), the self-assembled nanofibers form an anisotropic hydrogel string under modest shear stress. The anisotropic texture was further crosslinked by oxidative polymerization of DOPA residues and pushed to a new level for tissue regeneration. Collagen forms trimeric helical structures with various thermal stability, which is highly related to the residue substitutions. In our CMP design for collagen covalent capture, lysine and aspartate were employed in a trimeric helical structure to form axial salt-bridges. By utilizing carbodiimide-mediated amidation between amine and carboxylate, the crosslinked collagen helical dimers and trimers were observed on MALDI-TOF MS. Lastly, we attempted to design customized CMPs for natural collagen targeting. Based on different sequences of host natural collagens, the guest CMPs contain substitutions to maximize pairwise interactions, including charge pairs and cation-pi pairs. The CMP design was demonstrated to form destabilized collagen helical structure, but failed to hybridize with the synthetic natural collagen. Through the exploration of different host peptides, we believe this strategy would provide an advanced model once a complete understanding of substitution effect in collagen is given. | en_US |
| dc.format.mimetype | application/pdf | en_US |
| dc.identifier.citation | Li, I-Che. "Design of Multidomain Peptides and Collagen Mimetic Peptides for Biological Applications." (2018) Diss., Rice University. <a href="https://hdl.handle.net/1911/105716">https://hdl.handle.net/1911/105716</a>. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1911/105716 | en_US |
| dc.language.iso | eng | en_US |
| dc.rights | Copyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder. | en_US |
| dc.subject | Supramolecular chemistry | en_US |
| dc.subject | self-assembly | en_US |
| dc.subject | hydrogel | en_US |
| dc.subject | collagen | en_US |
| dc.title | Design of Multidomain Peptides and Collagen Mimetic Peptides for Biological Applications | en_US |
| dc.type | Thesis | en_US |
| dc.type.material | Text | en_US |
| thesis.degree.department | Chemistry | en_US |
| thesis.degree.discipline | Natural Sciences | en_US |
| thesis.degree.grantor | Rice University | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | Doctor of Philosophy | en_US |
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