Genetic Code Expansion using Aminoacylated Orthogonal tRNAs in Conjunction with Aminoacyl Sulfamides
Xiao Liang1, Ravil Khaybullin2, Junjie Fu3, Kevin Goncalves4, Amy Xia5, Xin Qi6
1Xiao Liang, Department of Medicinal Chemistry, University of Florida, College of Pharmacy, Gainesville, FL 32610, USA.
2Ravil Khaybullin, Department of Medicinal Chemistry, University of Florida, College of Pharmacy, Gainesville, FL 32610, USA.
3Junjie Fu, Department of Medicinal Chemistry, University of Florida, College of Pharmacy, Gainesville, FL 32610, USA.
4Kevin Goncalves, Department of Medicinal Chemistry, University of Florida, College of Pharmacy, Gainesville, FL 32610, USA.
5Amy Xia, Columbia University, New York, 10027, USA.
6Xin Qi, Department of Medicinal Chemistry, University of Florida, College of Pharmacy, Gainesville, FL 32610, USA.
Manuscript received on 20 January 2015 | Revised Manuscript received on 28 January 2015 | Manuscript published on 30 January 2015 | PP: 78-82 | Volume-3 Issue-6, January 2015 | Retrieval Number: F1323013615/2015©BEIESP
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© The Authors. Blue Eyes Intelligence Engineering and Sciences Publication (BEIESP). This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Abstract: Re-engineering the protein synthesis apparatus is a powerful approach to expand our understanding of the central macromolecular synthesis machinery present in all cells. In the current study, we showed that the high-affinity inhibitor—aminoacyl sulfamide significantly inhibited the activity of specific aminoacyl tRNA synthetase (aaRS), thereby creating synthetic gaps in the genetic code that can be filled with chemically aminoacylated orthogonal tRNAs. We further demonstrated the restoration of globin translation and enhancement of unnatural amino acids incorporation by biocytin-tRNAs coding for valine in the presence of Val-sulfamide. Taken together, this study demonstrates that we can create and reprogram synthetic “gaps” in the genetic code and provides an experimental means to pursue fundamental questions relating to the construction and expansion of the genetic code to facilitate the enrichment of desired unnatural amino acid residues.
Keyword: Aminoacyl Sulfamids, Aminoacylated Orthogonal TRNAs, Genetic code expansion.
Scope of the Article: Algorithm Engineering