Synthesis, Structure and Function Studies of Selenium and Tellurium Derivatized Nucleic Acids

Nucleic acids play important roles in living systems by storing and transferring genetic information and directing protein synthesis. Recently, it was found that nucleic acids can catalyze chemical and biochemical reactions similar to protein enzymes. In addition, they can also serve as drug targets...

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Main Author: Sheng, Jia
Format: Others
Published: Digital Archive @ GSU 2009
Subjects:
RNA
DNA
Online Access:http://digitalarchive.gsu.edu/chemistry_diss/30
http://digitalarchive.gsu.edu/cgi/viewcontent.cgi?article=1029&context=chemistry_diss
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spelling ndltd-GEORGIA-oai-digitalarchive.gsu.edu-chemistry_diss-10292013-04-23T03:18:15Z Synthesis, Structure and Function Studies of Selenium and Tellurium Derivatized Nucleic Acids Sheng, Jia Nucleic acids play important roles in living systems by storing and transferring genetic information and directing protein synthesis. Recently, it was found that nucleic acids can catalyze chemical and biochemical reactions similar to protein enzymes. In addition, they can also serve as drug targets for the treatment of deadly diseases such as AIDS and cancers. As a result, the 3D structure study of nucleic acids and proteinnucleic acids complexes by X-ray crystallography has become one of the most active research areas. However, the two intrinsic bottlenecks of macromolecule X-ray crystallography, including crystallization and phase determination, have significantly limited its application in study and discovery of the new structures and folds, as well as in exploration of the biological mechanisms. So far, the selenium derivatization (Se-Met) of proteins and multiple anomalous dispersion (MAD) or single anomalous dispersion (SAD) technology have revolutionized the protein crystallography field by providing a rational solution to solve the phase determination problem. Similarly, it’s important and urgent to develop a corresponding methodology for nucleic acid X-ray crystallography. The work presented here includes two general research directions: the selenium derivatized nucleic acids (SeNA) and tellurium derivatized nucleic acids (TeNA): 1) The SeNA strategy by site-specifically replacing oxygen with selenium at the 2’ and 4 positions of thymidine and uridine has been developed. We found that the selenium derivatization at both sites are relatively stable and doesn’t cause significant structure perturbations by comparing with their corresponding native counterparts. In addition to the phase determination, the 2’-Se modification can also facilitate crystal growth of many oligonucleotides. Moreover, we have observed colorful DNAs and RNAs with the 4-Se modification for the first time. 2) The TeNA strategy by covalently incorporating tellurium functionalities into different positions of nucleic acids, particularly at the 2’ and 5 position of thymidine, has been developed. We have demonstrated the compatibility of the tellurium modification and solid-phase synthesis, as well as the potential application of the tellurium modifications in anti-viral drug synthesis and DNA-damage investigation. 2009-04-21 text application/pdf http://digitalarchive.gsu.edu/chemistry_diss/30 http://digitalarchive.gsu.edu/cgi/viewcontent.cgi?article=1029&context=chemistry_diss Chemistry Dissertations Digital Archive @ GSU 3D-structure RNA DNA Nucleic acids Tellurium Selenium X-ray Chemistry
collection NDLTD
format Others
sources NDLTD
topic 3D-structure
RNA
DNA
Nucleic acids
Tellurium
Selenium
X-ray
Chemistry
spellingShingle 3D-structure
RNA
DNA
Nucleic acids
Tellurium
Selenium
X-ray
Chemistry
Sheng, Jia
Synthesis, Structure and Function Studies of Selenium and Tellurium Derivatized Nucleic Acids
description Nucleic acids play important roles in living systems by storing and transferring genetic information and directing protein synthesis. Recently, it was found that nucleic acids can catalyze chemical and biochemical reactions similar to protein enzymes. In addition, they can also serve as drug targets for the treatment of deadly diseases such as AIDS and cancers. As a result, the 3D structure study of nucleic acids and proteinnucleic acids complexes by X-ray crystallography has become one of the most active research areas. However, the two intrinsic bottlenecks of macromolecule X-ray crystallography, including crystallization and phase determination, have significantly limited its application in study and discovery of the new structures and folds, as well as in exploration of the biological mechanisms. So far, the selenium derivatization (Se-Met) of proteins and multiple anomalous dispersion (MAD) or single anomalous dispersion (SAD) technology have revolutionized the protein crystallography field by providing a rational solution to solve the phase determination problem. Similarly, it’s important and urgent to develop a corresponding methodology for nucleic acid X-ray crystallography. The work presented here includes two general research directions: the selenium derivatized nucleic acids (SeNA) and tellurium derivatized nucleic acids (TeNA): 1) The SeNA strategy by site-specifically replacing oxygen with selenium at the 2’ and 4 positions of thymidine and uridine has been developed. We found that the selenium derivatization at both sites are relatively stable and doesn’t cause significant structure perturbations by comparing with their corresponding native counterparts. In addition to the phase determination, the 2’-Se modification can also facilitate crystal growth of many oligonucleotides. Moreover, we have observed colorful DNAs and RNAs with the 4-Se modification for the first time. 2) The TeNA strategy by covalently incorporating tellurium functionalities into different positions of nucleic acids, particularly at the 2’ and 5 position of thymidine, has been developed. We have demonstrated the compatibility of the tellurium modification and solid-phase synthesis, as well as the potential application of the tellurium modifications in anti-viral drug synthesis and DNA-damage investigation.
author Sheng, Jia
author_facet Sheng, Jia
author_sort Sheng, Jia
title Synthesis, Structure and Function Studies of Selenium and Tellurium Derivatized Nucleic Acids
title_short Synthesis, Structure and Function Studies of Selenium and Tellurium Derivatized Nucleic Acids
title_full Synthesis, Structure and Function Studies of Selenium and Tellurium Derivatized Nucleic Acids
title_fullStr Synthesis, Structure and Function Studies of Selenium and Tellurium Derivatized Nucleic Acids
title_full_unstemmed Synthesis, Structure and Function Studies of Selenium and Tellurium Derivatized Nucleic Acids
title_sort synthesis, structure and function studies of selenium and tellurium derivatized nucleic acids
publisher Digital Archive @ GSU
publishDate 2009
url http://digitalarchive.gsu.edu/chemistry_diss/30
http://digitalarchive.gsu.edu/cgi/viewcontent.cgi?article=1029&context=chemistry_diss
work_keys_str_mv AT shengjia synthesisstructureandfunctionstudiesofseleniumandtelluriumderivatizednucleicacids
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