Author ORCID Identifier

https://orcid.org/0000-0002-6144-4372

Date of Award

8-13-2019

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Zhen Huang

Abstract

There are two major challenges in nucleic acid X-ray crystallography: crystallization and phasing determination. With the introduction of selenium modification, the phasing problem can be solved rationally, while the crystallization problem can be solved partially. By taking advantage of the selenium modification, herein we report the synthesis of the Se-DNAs and the thermostability and crystallization study of the DNA-small molecule complexes. 5-Se-thymidine was successfully synthesized and incorporated into DNA oligonucleotides via solid-phase synthesis in order to facilitate the crystallization and phasing. The UV-melting study reveals that the selenium modification has caused no significate perturbation to the DNA stability. The small molecules (DB2429 and DB2457) were co-crystalized with Se-DNAs and the Se-DNA crystals were obtained, which are better than the native ones. In addition, our research suggested that the DNA oligonucleotides with the 5’-overhang form better crystals than those with the 3’-overhang or non-overhang. Our X-ray diffraction study is in progress.

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