Selenium derivatization (via selenomethionine) of proteins for crystal structure determination via MAD phasing has revolutionized protein X-ray crystallography. It is estimated that over two thirds of all new crystal structures of proteins have been determined via Se-Met derivatization. Similarly, selenium functionalities have also been successfully incorporated into nucleic acids to facilitate their structure studies and it has been proved that this Se-derivatization has advantages over halogen strategy, which was usually used as a traditional method in this field. This review reports the development of site-specific selenium derivatization of nucleic acids for phase determination since the year of 2001 (mainly focus on the 2’-position of the ribose). All the synthesis of 2’-SeMe modified phosphoramidite building blocks (U, C, T, A, G) and the according oligonucleotides are included. In addition, several structures of selenium contained nucleic acid are also described in this paper.
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