Material Information
- Title:
- Copper(I)-Catalyzed Azide-Alkyne Cycloadditions for Functionalization of Enzyme Packaged Viral Nanoparticles
- Physical Description:
- Book
- Language:
- English
- Creator:
- Hincapie, Robert
- Publisher:
- New College of Florida
- Place of Publication:
- Sarasota, Fla.
- Publication Date:
- 2014
Thesis/Dissertation Information
- Degree:
- Bachelor's ( B.A.)
- Degree Grantor:
- New College of Florida
- Degree Divisions:
- Natural Sciences
- Area of Concentration:
- Chemistry
Subjects
- Genre:
- bibliography ( marcgt )
theses ( marcgt )
government publication (state, provincial, territorial, dependent) ( marcgt )
born-digital ( sobekcm )
Electronic Thesis or Dissertation
Notes
- Abstract:
- There is an unfulfilled need for drug delivery systems that exhibit a high
degree of efficacy while minimizing systemic toxicity. The strategy of delivering
chemotherapeutic agents through the use of protein nanoparticles allows users to
modulate properties of the delivery agent by chemical and genetic means. Virus
protein shells offer unique advantages, since the polyvalency and symmetry
of the virus macrostructure can be exploited to present multiple copies of
functional targeting ligands in high density. Our goal was to prepare QB virus particles encapsulating the enzyme
cytosine deaminase (QB@CD) and to attach functional groups to the particles
via a two-step chemical modifification. First, functional groups were incorporated
via N-hydroxysuccinimide ester chemistry and then a targeting motif was
appended via the copper-catalyzed azide-alkyne cycloaddition (CuAAC), the
quintessential click reaction. The packaged enzyme retained 55.3 + 3.2 % of its
original kinetic activity following the NHS-alkylation step, but only 7.0 + 0.3 %
of its activity following exposure to copper(I) during the CuAAC. Next, we sought to find conditions for performing the click reaction on
enzyme-packaged particles without inhibiting the enzyme. Enzyme inhibition
was mitigated when a high affinity Cu-binding ligand (BimC4A) and low
clicking temperatures were employed. After exploring a range of other clicking
conditions, we were able to push the low-temperature on-particle click reaction
to 8.1 + 0.8 % completion while retaining 22.1 + 1.2 % of the activity of QB@CD.
Only a small subset of compatible reaction conditions were explored in
this project, so further optimization is necessary to accomplish the desired
goal. The copper affinity of ligands must be finely tuned to prevent enzyme
inhibition without significantly slowing the rate of the click reaction.
- Statement of Responsibility:
- by Robert Hincapie
- Thesis:
- Thesis (B.A.) -- New College of Florida, 2014
- General Note:
- RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE
- Bibliography:
- Includes bibliographical references.
- General Note:
- This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
- General Note:
- Faculty Sponsor: Walstrom, Katherine
Record Information
- Source Institution:
- New College of Florida
- Holding Location:
- New College of Florida
- Rights Management:
- Applicable rights reserved.
- Classification:
- S.T. 2014 H5
- System ID:
- AA00024750:00001
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