Development of Bioactive Collagen Mimetic Peptides (CMPs) Using Supramolecular and Covalent Techniques
| dc.contributor.advisor | Hartgerink, Jeffrey D | en_US |
| dc.creator | Peterson, Caroline M | en_US |
| dc.date.accessioned | 2023-08-09T19:21:13Z | en_US |
| dc.date.created | 2023-05 | en_US |
| dc.date.issued | 2023-04-20 | en_US |
| dc.date.submitted | May 2023 | en_US |
| dc.date.updated | 2023-08-09T19:21:13Z | en_US |
| dc.description.abstract | Collagen mimetic peptides (CMPs) are an excellent tool for studying both the structure and function of natural collagen. Total synthetic control of the amino acid sequence allows for the deliberate manipulation of the triple helical structure. The ability to engineer CMPs with structural modifications directly influences the ability to mimic collagen biological function. In Chapter 1 the use of CMPs to model collagen primary, secondary, tertiary and quaternary structures is evaluated. The utility of CMPs to model collagen-receptor interactions and the current uses of CMPs in biomaterials are discussed. The synthesis of highly specific and stable heterotrimeric triple helices is very challenging. Chapter 2 details the principles that guide the design of these peptides. Elements of positive and negative design, including supramolecular charge pairs and single residue substitutions were used in combination with a computational algorithm to obtain a single register and composition ABC heterotrimer. This peptide design was then used as a heterotrimeric template to evaluate the utility of new pairwise interactions. Although supramolecular interactions are a great tool for driving the assembly of the triple helix, frequently it is desirable to form covalent bonds between the strands to increase the stability and fasten the folding of CMPs. Chapter 3 is a detailed study of the covalent capture of CMPs. The effects of the number and placement of isopeptide bonds are evaluated. Also, for the first time the differences between covalently linked frame shifted CMPs are studied. Several trends are identified, which will inform the ideal use of covalent bonds in CMPs. Chapter 4 details a study on how the structure of CMPs directly impacts biological activity. A CMP with the integrin binding motif “GFOGER” is designed and tested for cell adhesion before and after covalent capture. The establishment of covalent bonds between the strands of the triple helix results in increased integrin binding, demonstrating the need for synthetic methods to “lock” the triple helical structure. Chapter 5 describes the efforts to incorporate this integrin binding CMP into two different materials. To functionalize a peptide hydrogel with the CMP, a click chemistry approach is used. The sequence of the CMP was modified with an alkyne, which does not disrupt the tertiary structure. After covalent capture, this CMP can be conjugated to an azide bearing peptide fragment. To functionalize liposomes with the integrin binding CMP, a peptide amphiphile was designed. Despite the presence of the hydrophobic tail, this CMP can still successfully undergo covalent capture. Incorporation of the CMP into these materials may increase their interactions with cells. Finally, in Chapter 6 covalent capture is used to synthesize a library of stabilized peptide mimics of Surfactant Protein A (SP-A). These peptides are screened for cell adhesion, and several important residues are identified. CMPs can successfully mimic the interactions between innate immune proteins and their receptors. | en_US |
| dc.embargo.lift | 2024-05-01 | en_US |
| dc.embargo.terms | 2024-05-01 | en_US |
| dc.format.mimetype | application/pdf | en_US |
| dc.identifier.citation | Peterson, Caroline M. "Development of Bioactive Collagen Mimetic Peptides (CMPs) Using Supramolecular and Covalent Techniques." (2023) Diss., Rice University. <a href="https://hdl.handle.net/1911/115188">https://hdl.handle.net/1911/115188</a>. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1911/115188 | 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 | Self-assembly | en_US |
| dc.subject | Supramolecular | en_US |
| dc.subject | Covalent capture | en_US |
| dc.subject | Collagen | en_US |
| dc.subject | Peptides | en_US |
| dc.title | Development of Bioactive Collagen Mimetic Peptides (CMPs) Using Supramolecular and Covalent Techniques | 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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