Nucleic acids are fundamental building blocks of living systems’ genetic information, and are also responsible for regulating organisms’ protein synthesis, catalysis, etc. To better understand nucleic acids’ functions and working mechanisms, it is essential to obtain their structures. So far, the most common and powerful method to reveal the structures of macromolecules is X-ray crystallography. However, for nucleic acids structure determination, two problems are to be solved using such technology – crystallization and phasing. Selenium modification of nucleic acids has been proven to help address the two problems from native ones, without drastically affect their conformations. Also, previous studies suggest selenium modification enhances specific base pairing, especially against U-G wobble pair. With such feature, modified nucleic acids may be utilized by sequence-based diagnostics and therapies.

In this thesis, synthesis of 2’-arabino SeMe modified thymine is discussed. Such modification is believed to be compatible with B-form DNA structure determination.