?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F33174%2F&rft.title=Supramolecular+Architectures+and+Mimics+of+Complex+Natural+Folds+Derived+from+Rationally+Designed+%CE%B1-Helical+Protein+Structures&rft.creator=Tavenor%2C+Nathan&rft.description=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%3A+collagen%2C+microtubules%2C+viral+capsids%2C+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%2C+protein-based+SMPs+form+due+to+self-assembly+driven+by+intermolecular+interactions+between+monomers%2C+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.++%0D%0AThe+central+hypothesis+underlying+our+work+is+that+%CE%B1-helical+coiled+coils%2C+a+well-studied+protein+quaternary+folding+motif%2C+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%2For+peptide+sequence%2C+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%2C+stability%2C+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.%0D%0ASeparate+from+the+above+efforts+on+supramolecular+architectures+was+work+on+improving+backbone+modification+strategies+for+an+%CE%B1-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+(%CE%B2-sheet%2C+%CE%B1-helix%2C+loops+and+%CE%B2-turns)+of+a+small+protein+with+a+tertiary+fold.+Although+the+tertiary+fold+of+the+native+sequence+was+mimicked+by+the+resulting+artificial+protein%2C+the+thermodynamic+stability+was+greatly+compromised.+Most+of+this+energetic+penalty+derived+from+the+modifications+present+in+the+%CE%B1-helix.+The+contribution+within+this+thesis+was+direct+comparison+of+several+%CE%B1-helical+design+strategies+and+establishment+of+the+thermodynamic+consequences+of+each.&rft.date=2017-09-28&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F33174%2F7%2Ftavenorna_etd2017_revised5.pdf&rft.identifier=++Tavenor%2C+Nathan++(2017)+Supramolecular+Architectures+and+Mimics+of+Complex+Natural+Folds+Derived+from+Rationally+Designed+%CE%B1-Helical+Protein+Structures.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++