Ce YangFollow

Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)



First Advisor

Binghe Wang

Second Advisor

Suazette Mooring

Third Advisor

Samer Gozem


This dissertation studies the applications of prodrug strategies in drug delivery. The prodrugs under study are compounds that can deliver carbon monoxide or PROTACs under physiological conditions.

Chapter 1 describes a new structural scaffold of CO prodrugs through the use of an adamantane moiety to afford stabilization of a critical precursor structure, cyclopentadienone, and to allow for optimization of water solubility. The prodrugs are tested in a cell culture model to confirm CO release from such prodrugs and demonstrate their efficacy in anti-inflammation studies.

Chapter 2 reviews the field of using click chemistry in the development of PROTACs, which are hetero-bifunctional molecules designed to mediate the disposal of a target protein via recruitment of the ubiquitination-proteasome degradation machinery. Click chemistry has unique advantages for tethering two or more molecular entities of choice under near-physiological conditions and therefore has been applied to the development of PROTACs in various ways. Chapter 2 provides a succinct summary of this field with a critical analysis of various factors that need to be considered for optimal results.

Chapter 3 describes our effort to develop a reversible assembly approach to the design of PROTACS.


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