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dc.contributor.advisorSchafmeister, Christian
dc.creatorNorthrup, Justin David
dc.date.accessioned2020-11-04T17:00:51Z
dc.date.available2020-11-04T17:00:51Z
dc.date.issued2016
dc.identifier.other974918978
dc.identifier.urihttp://hdl.handle.net/20.500.12613/3343
dc.description.abstractBinding to protein surfaces or shallow grooves with synthetic molecules poses a unique challenge, since this inherently requires large areas to facilitate interactions. Peptoids have been shown to interact with proteins, and combinatorial libraries of peptoids have been proven to be effective in discovering new ligands for protein binding. Unfortunately, most peptoids are flexible and lack the surface area required to compete with larger protein interactions. To combat these problems, we have created spiroligomers that have a rigid backbone, exhibit functionality comparable to proteins, and are resistant to proteases. To facilitate the rapid installment of spiroligomers into peptoid subunits, we required a more streamlined approach for functionalization of spiroligomers. To this end we applied a single-pot alkylation method, with which we installed over 25 unique functional groups onto different spiroligomer hydantoins. These spiroligomer hydantoins are spirocycles that possesses two stereocenters, of which we have complete control, as well as a protected proline amino acid. These new proline amino acids (enhanced prolines) have been incorporated into peptides via Fmoc-SPPS. Finally, we have functionalized these enhanced proline residues with another functional group and a protected primary amine, which allow for their use in peptoid synthesis. We developed methods to tether multiple spiroligomers together utilizing a peptoid backbone, as well as being able to incorporate spiroligomers into peptoid macrocycles. These spiroligomer-peptoid hybrids are large, diverse, and preorganized structures that have a large potential interacting surface area for binding to protein surfaces or shallow grooves.
dc.format.extent416 pages
dc.language.isoeng
dc.publisherTemple University. Libraries
dc.relation.ispartofTheses and Dissertations
dc.rightsIN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectChemistry, Organic
dc.subjectHydantoin
dc.subjectPeptide
dc.subjectPeptidomimetic
dc.subjectPeptoid
dc.subjectProline
dc.subjectSpiroligomer
dc.titleThe Design and Synthesis of Peptidomimetic-Hybrids: Expanding Spiroligomers, Peptoids, and Proline
dc.typeText
dc.type.genreThesis/Dissertation
dc.contributor.committeememberVoelz, Vincent
dc.contributor.committeememberDobereiner, Graham
dc.contributor.committeememberChilders, Wayne E.
dc.description.departmentChemistry
dc.relation.doihttp://dx.doi.org/10.34944/dspace/3325
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.degreePh.D.
refterms.dateFOA2020-11-04T17:00:51Z


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