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Oligopeptide-functionalized Graft Copolymers: Synthesis and Applications in Nucleic Acid Delivery

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dc.contributor.advisorTodd S. Emrick
dc.contributor.advisorMurugappan Muthukumar
dc.contributor.advisorCraig T. Martin
dc.contributor.authorBreitenkamp, Rebecca Boudreaux
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.date2023-09-22T20:06:15.000
dc.date.accessioned2024-04-26T19:50:20Z
dc.date.available2024-04-26T19:50:20Z
dc.date.issued2009-02-01
dc.description.abstractUtilizing the diverse functionality of amino acids, a new class of amphiphilic graft copolymers has been synthesized, characterized, and explored for applications in biomaterials and nucleic acid delivery. This thesis research focused on the syntheses of oligopeptide-functionalized polyesters and polyolefins. Polyester functionalization was geared towards applications in biomaterials, tissue engineering, and drug delivery by incorporating sequences that promote cell-adhesion. These polyester- graft -oligopeptide materials were prepared by a 1,3-Huisgen cycloaddition reaction, "click" chemistry, of an azide-terminated oligopeptide (prepared by Fmoc-based solid phase peptide synthesis (SPPS)) and alkyne-containing polyester (synthesized by ring-opening polymerization). Following the syntheses of these materials, they were analyzed by nuclear magnetic resonance (NMR) and organic gel permeation chromatography (GPC). The oligopeptide-functionalized polyolefins were designed for nucleic acid complexation, and therefore the oligopeptide sequences were intended to incorporate positively-charged moieties ( e.g. , oligolysine) for DNA and short interfering RNA (siRNA) complexation. These graft copolymers, prepared by SPPS followed by ring-opening metathesis polymerization, have highly tunable structures that enable control over charge density and polymer backbone rigidity. Moreover, non-ionic hydrophilic grafts such as polyethylene glycol were integrated into these polyelectrolytes such that the charges along the polymer backbone are spaced accordingly while maintaining the hydrophilicity of the polymer. While numerous applications for such charged, "bio-tailored" materials can be envisioned, this work is geared towards positively-charged polyelectrolytes for their potential application in nucleic acid therapy, specifically the delivery of plasmid DNA and siRNA. These graft copolymers were characterized ( 1 H, 13 C NMR, organic and aqueous GPC), studied for their solution properties (static and dynamic light scattering), and investigated as polyplexes with plasmid DNA.
dc.description.degreeDoctor of Philosophy (PhD)
dc.description.departmentPolymer Science and Engineering
dc.identifier.doihttps://doi.org/10.7275/e3j6-5521
dc.identifier.urihttps://hdl.handle.net/20.500.14394/38949
dc.relation.urlhttps://scholarworks.umass.edu/cgi/viewcontent.cgi?article=1005&context=open_access_dissertations&unstamped=1
dc.source.statuspublished
dc.subjectAmphiphilic graft copolymers
dc.subjectFunctionalized polyesters
dc.subjectGene delivery
dc.subjectNucleic acid delivery
dc.subjectOligopeptides
dc.subjectRing-opening metathesis polymerization
dc.subjectMaterials Science and Engineering
dc.subjectPolymer and Organic Materials
dc.titleOligopeptide-functionalized Graft Copolymers: Synthesis and Applications in Nucleic Acid Delivery
dc.typedissertation
dc.typearticle
dc.typedissertation
digcom.contributor.authorisAuthorOfPublication|email:Rebecca.Breitenkamp@gmail.com|institution:University of Massachusetts Amherst|Breitenkamp, Rebecca Boudreaux
digcom.identifieropen_access_dissertations/5
digcom.identifier.contextkey905295
digcom.identifier.submissionpathopen_access_dissertations/5
dspace.entity.typePublication
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