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Polymeric Peptide Mimics for Protein Delivery

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dc.contributor.advisorGregory N. Tew
dc.contributor.authorBacklund, Coralie
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.date2023-09-23T21:17:24.000
dc.date.accessioned2024-04-26T15:23:09Z
dc.date.available2024-04-26T15:23:09Z
dc.date.submittedMay
dc.date.submitted2018
dc.description.abstractThe plasma membrane is a major obstacle in the development and use of biomacromolecules for intracellular applications. Consequently, proteins with intracellular targets represent an enormous, yet under studied avenue for therapeutics. Extended research has aimed at facilitating intracellular delivery of exogenous proteins using protein transduction domains (PTDs), which allow transport of bioactive molecules into cells. Synthetic polymers, inspired by PTDs, provide a well-controlled platform to vary molecular architecture for structure activity relationship studies. Specifically, this thesis focuses on the use of ring-opening metathesis, a facile and efficient polymerization technique, through which we can vary structural parameters to optimize delivery of non-covalently encapsulated proteins. The aim was to characterize, optimize, and utilize PTD mimics (PTDMs) for functional protein delivery. Fluorescently labeled cargo were used to elucidate the predominant cellular entry mechanism for the PTDMs and were compared to their ability to deliver protein into cells. A series of polymers was designed around the most membrane active polymers to explore the incorporation of guanidine and hydrophobic moieties, yielding a PTDM capable of high protein delivery into a variety of cell types. The PTDM was then explored for use as a vaccine delivery reagent into immune cells. The ability to have a specific response with the cargo of interest verifies cytosolic delivery using the PTDMs and provides valuable insight into their use to affect intracellular pathways.
dc.description.degreeDoctor of Philosophy (PhD)
dc.description.departmentPolymer Science and Engineering
dc.identifier.doihttps://doi.org/10.7275/pmkg-tj22
dc.identifier.orcidN/A
dc.identifier.urihttps://hdl.handle.net/20.500.14394/17411
dc.relation.urlhttps://scholarworks.umass.edu/cgi/viewcontent.cgi?article=2360&context=dissertations_2&unstamped=1
dc.source.statuspublished
dc.subjectCell Penetrating Peptide Mimics
dc.subjectProtein Transduction Domain Mimics
dc.subjectProtein Delivery
dc.subjectBiological Engineering
dc.subjectBiomaterials
dc.subjectImmunoprophylaxis and Therapy
dc.subjectPolymer Chemistry
dc.titlePolymeric Peptide Mimics for Protein Delivery
dc.typeopenaccess
dc.typearticle
dc.typedissertation
digcom.contributor.authorisAuthorOfPublication|email:backlund@umass.edu|institution:University of Massachusetts Amherst|Backlund, Coralie
digcom.identifierdissertations_2/1216
digcom.identifier.contextkey11960156
digcom.identifier.submissionpathdissertations_2/1216
dspace.entity.typePublication
relation.isAuthorOfPublication808e4835-2f0b-4982-ad8f-91e610eefde9
relation.isAuthorOfPublication.latestForDiscovery808e4835-2f0b-4982-ad8f-91e610eefde9
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