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Copper(I)-Catalyzed Azide-Alkyne Cycloadditions for Functionalization of Enzyme Packaged Viral Nanoparticles

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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:

Thesis/Dissertation Information

Degree:
Bachelor's ( B.A.)
Degree Grantor:
New College of Florida
Degree Divisions:
Natural Sciences
Area of Concentration:
Chemistry
Faculty Sponsor:
Walstrom, Katherine

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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