Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Chemistry

Language

English (en)

Date of Award

1-1-2011

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

John Taylor

Abstract

Peptide Nucleic Acids: PNAs), are an ideal choice for antisense and antigene tools and probes because of their stability and high binding affinity, but have limited application as therapeutic and diagnostic agents because of poor membrane permeability. To increase membrane permeability, we conjugated hydrophobic lipids or phospholipid molecules and hydrophilic cell penetrating peptides to the N and C terminus of PNAs, and studied their physical and biological properties. After solid-phase automated synthesis, PNA-CPPs: TAT/Arg9) were coupled with lipids or phospholipids before cleavage from the support and then purified by HPLC. The conjugates were characterized by UV-vis and MALDI, and by their ability to form vesicles in water and to partition between water and octanol. The size of the vesicles formed was determined by DLS. One of the Lipid-PNA-TAT conjugates was further tested in vivo as a potential PET imaging reagent after radiolabeling with bromine-76.

Comments

Permanent URL: http://dx.doi.org/10.7936/K77942Q8

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