Date of Award

8-2016

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

Committee Member

Bill Pennington, Committee Chair

Committee Member

Modi Wetzler, Co-Chair

Committee Member

Andrew Tennyson

Committee Member

Daniel Whitehead

Committee Member

Rhett Smith

Abstract

Part 1:

Peptoids are isomers of peptides where the side chains are on the nitrogens instead of the carbons, which have been developed for a variety of biomedical, nano, and materials applications. Conventional peptoid synthesis uses molar concentrations of reagents and hours of reaction time per residue, thus practically limiting the lengths of peptoids. Recently, we have managed to improve yields and make peptoids of unprecedented lengths while reducing the reaction times and concentrations of reagents. Indeed, we have demonstrated that the conventional longer reaction times degrade the peptoids and lead to lower purities. In addition, by using microwave conditions, we successfully incorporate sterically bulky, chiral side chains into peptoids at concentrations lower than have ever been reported. We hereby report the longest peptoid ever synthesized, a 120-mer decablock copolymer that is nearly perfectly monodisperse without any purification.

Part 2:

Creatine is a nitrogen-containing compound that helps supply energy to the cells in the body. This is done by accepting a phosphate from excess ATP to form phosphocreatine which is used to replenish ATP when needed. Half of the creatine in adults is obtained through their diet while the other half is synthesized by the body. However, creatine requires a transporter to cross the blood brain barrier (BBB) and mutation in the gene encoding for the creatine transporter, slc6a8 (creatine transporter deficiency, CTD) causes severe X-linked intellectual disability which accounts for approximately 2% of all X-Linked Intellectual Deficiency patients. CTD causes developmental delays, seizures, autistic features, speech impairment, brain atrophy and intellectual disabilities. Without a working creatine transporter, creatine cannot pass through BBB, therefore, analogs of creatine derivatives that could more readily diffuse through the BBB could potentially be used to treat CTD. Hence, the focus for this project was to synthesize creatine derivatives that could potentially cross the BBB without the need of a creatine transporter. This was done by modifying the creatine with substituents that are hydrophobic so that the derivative becomes lipophilic enough to cross the BBB.

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Chemistry Commons

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