Date of Award

5-2014

Degree Type

Dissertation

Degree Name

PhD. Chemistry

Department

Chemistry and Biochemistry

Advisor

James E. Hanson, Ph.D.

Committee Member

Cecilia Marzabadi, Ph.D.

Committee Member

Cosimo Antonacci, Ph.D.

Committee Member

Nicholas H. Snow, Ph.D.

Keywords

Quadruplex DNA, Synthesis of Cationic Porphyrins, DNA Binding, EDC Coupling Reactions, DNA Binding Polymers, Quadruplex Binding Ligands

Abstract

Molecular recognition is vital to many biochemical processes and is at the heart of promising bio-medically related technologies. Molecular imprinting has a long-standing history as a successful method for mimicking the molecular recognition phenomena exhibited by nature, whereby artificial receptors are prepared for a given target molecule based on synthetic polymers. The molecularly imprinted polymer (MIP) contains a three dimensional network with a memorized cavity specific to the shape and functionality of the templated target molecule. The utility of traditional MIPs has been limited due to an inherent lack of solubility. We have worked toward developing a system that allows for the preparation of soluble MIPs targeting quadruplex DNA, specifically the human telomeric repeat (TTAGGG)4. To do so we have synthesized a series of meso-substituted, water soluble, tetracationic pyridinium porphyrins which we have successfully coupled to polyethyleneimine (PEI), forming a condensation polyamide. We have demonstrated that one of these porphyrins can be used as an efficient polymer cross-linker, which provides a unique quadruplex DNA binding site in the polymer network. Unfortunately, the high cationic charge density found on PEI has been found to elicit potential dilemmas in the utility of this method. Attempts have been made to reduce this charge by increasing the cross-linking agent and partially acetylating the PEI. While the network structure of this soluble cross-linked polymer still requires optimization, it has shown promise and demonstrates the opportunities for new soluble molecularly imprinted polymer designs that include quadruplex binding sites.

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