Date of Award


Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Administrative Home Department

Department of Chemistry

Advisor 1

Shiyue Fang

Committee Member 1

Tarun K. Dam

Committee Member 2

Lanrong Bi

Committee Member 3

Qing-Hui Chen


Over the past decades, researchers have tried various chemical methods to synthesize modified oligodeoxynucleotides (ODNs, i.e. short segments of DNAs). Traditional ODN synthesis methods require strong basic, and nucleophilic conditions for the deprotection and cleavage of the ODN from the solid support. However, the sensitive ODNs containing labile functionalities are vulnerable to such harsh conditions. Sensitive ODNs have a wide range of applications in research and pharmaceuticals. To synthesize sensitive ODNs, researchers devised different strategies but no practical methods have been developed. To overcome these challenges, we developed alkyl Dim alkyl Dmoc technology. This innovative technology uses weakly basic and non-nucleophilic conditions to synthesize the sensitive ODNs. To demonstrate the feasibility of alkyl Dim alkyl Dmoc technology different ODNs were synthesized, purified using RP-HPLC, and analyzed using MALDI-TOF MS and capillary electrophoresis. Using the method, we successfully synthesized various sensitive ODNs that cannot be synthesized or are highly challenging to synthesize using any known methods. The longest ODN synthesized using methyl Dmoc technology was 23-mer. To further extend the utility and capability of alkyl Dim alkyl Dmoc technology, we aimed to synthesize longer sensitive ODNs. To achieve this goal, PEGylated Dmoc (pDmoc) technology was developed. The introduction of the PEG Dmoc group increased the ODN solubility which facilitated the synthesis of longer ODNs. The longest ODN synthesized was a 49-mer. Moreover, a sensitive 4acC epigenetically modified ODN was synthesized. The success of synthesizing this naturally occurring sensitive ODN will make many projects in the area of epigenetics feasible.