Abstract/Details

Oligopeptide-functionalized graft copolymers: Synthesis and applications in nucleic acid delivery


2009 2009

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Abstract (summary)

Utilizing 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 (1H, 13C NMR, organic and aqueous GPC), studied for their solution properties (static and dynamic light scattering), and investigated as polyplexes with plasmid DNA.

Indexing (details)


Subject
Cellular biology;
Polymer chemistry
Classification
0379: Cellular biology
0495: Polymer chemistry
Identifier / keyword
Pure sciences; Biological sciences; Amphiphilic graft copolymers; Functionalized polyesters; Gene delivery; Nucleic acid delivery; Oligopeptides; Ring-opening metathesis polymerization
Title
Oligopeptide-functionalized graft copolymers: Synthesis and applications in nucleic acid delivery
Author
Breitenkamp, Rebecca Boudreaux
Number of pages
125
Publication year
2009
Degree date
2009
School code
0118
Source
DAI-B 70/03, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781109059212
Advisor
Emrick, Todd S.
Committee member
Martin, Craig T.; Muthukumar, Murugappan
University/institution
University of Massachusetts Amherst
Department
Polymer Science & Engineering
University location
United States -- Massachusetts
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3349711
ProQuest document ID
304927527
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304927527
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