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University of Pittsburgh

1. Tavenor, Nathan. Supramolecular Architectures and Mimics of Complex Natural Folds Derived from Rationally Designed α-Helical Protein Structures.

Degree: 2017, University of Pittsburgh

Protein-based supramolecular polymers (SMPs) are a class of biomaterials which draw inspiration from and expand upon the many examples of complex protein quaternary structures observed in nature: collagen, microtubules, viral capsids, etc. Designing synthetic supramolecular protein scaffolds both increases our understanding of natural superstructures and allows for the creation of novel materials. Similar to small-molecule SMPs, protein-based SMPs form due to self-assembly driven by intermolecular interactions between monomers, and monomer structure determines the properties of the overall material. Using protein-based monomers takes advantage of the self-assembly and highly specific molecular recognition properties encodable in polypeptide sequences to rationally design SMP architectures. The central hypothesis underlying our work is that α-helical coiled coils, a well-studied protein quaternary folding motif, are well-suited to SMP design through the addition of synthetic linkers at solvent-exposed sites. Through small changes in the structures of the cross-links and/or peptide sequence, we have been able to control both the nanoscale organization and the macroscopic properties of the SMPs. Changes to the linker and hydrophobic core of the peptide can be used to control polymer rigidity, stability, and dimensionality. The gaps in knowledge that this thesis sought to fill on this project were 1) the relationship between the molecular structure of the cross-linked polypeptides and the macroscopic properties of the SMPs and 2) a means of creating materials exhibiting multi-dimensional net or framework topologies. Separate from the above efforts on supramolecular architectures was work on improving backbone modification strategies for an α-helix in the context of a complex protein tertiary fold. Earlier work in our lab had successfully incorporated unnatural building blocks into every major secondary structure (β-sheet, α-helix, loops and β-turns) of a small protein with a tertiary fold. Although the tertiary fold of the native sequence was mimicked by the resulting artificial protein, the thermodynamic stability was greatly compromised. Most of this energetic penalty derived from the modifications present in the α-helix. The contribution within this thesis was direct comparison of several α-helical design strategies and establishment of the thermodynamic consequences of each.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Tavenor, N. (2017). Supramolecular Architectures and Mimics of Complex Natural Folds Derived from Rationally Designed α-Helical Protein Structures. (Thesis). University of Pittsburgh. Retrieved from http://d-scholarship.pitt.edu/33174/7/tavenorna_etd2017_revised5.pdf ; http://d-scholarship.pitt.edu/33174/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Tavenor, Nathan. “Supramolecular Architectures and Mimics of Complex Natural Folds Derived from Rationally Designed α-Helical Protein Structures.” 2017. Thesis, University of Pittsburgh. Accessed October 22, 2017. http://d-scholarship.pitt.edu/33174/7/tavenorna_etd2017_revised5.pdf ; http://d-scholarship.pitt.edu/33174/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Tavenor, Nathan. “Supramolecular Architectures and Mimics of Complex Natural Folds Derived from Rationally Designed α-Helical Protein Structures.” 2017. Web. 22 Oct 2017.

Vancouver:

Tavenor N. Supramolecular Architectures and Mimics of Complex Natural Folds Derived from Rationally Designed α-Helical Protein Structures. [Internet] [Thesis]. University of Pittsburgh; 2017. [cited 2017 Oct 22]. Available from: http://d-scholarship.pitt.edu/33174/7/tavenorna_etd2017_revised5.pdf ; http://d-scholarship.pitt.edu/33174/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tavenor N. Supramolecular Architectures and Mimics of Complex Natural Folds Derived from Rationally Designed α-Helical Protein Structures. [Thesis]. University of Pittsburgh; 2017. Available from: http://d-scholarship.pitt.edu/33174/7/tavenorna_etd2017_revised5.pdf ; http://d-scholarship.pitt.edu/33174/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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