Abstract

The long-term goal of this work is the elaboration and study of proteins containing synthetic amino acids at specific, predetermined positions. These are to be incorporated by read through of nonsense codons with misacylated suppressor tRNAs. For the period of requested support, we propose to prepare and study analogues of firefly luciferase, MAP kinase ERK2, and DNA polymerase beta. Also of interest is the exploitation of a new method for introducing a broader range of amino acid analogues into the derived proteins, and the elaboration of the modified proteins in an intact cellular system

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA077359-08
Application #
6873751
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Fu, Yali
Project Start
1998-04-01
Project End
2008-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
8
Fiscal Year
2005
Total Cost
$309,328
Indirect Cost

  Institution

Name
University of Virginia
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904

  Publications

Chen, Shengxi; Hecht, Sidney M (2008) Synthesis of pdCpAs and transfer RNAs activated with derivatives of aspartic acid and cysteine. Bioorg Med Chem 16:9023-31
Yakovleva, Lyudmila; Chen, Shengxi; Hecht, Sidney M et al. (2008) Chemical and traditional mutagenesis of vaccinia DNA topoisomerase provides insights to cleavage site recognition and transesterification chemistry. J Biol Chem 283:16093-103
Duca, Maria; Chen, Shengxi; Hecht, Sidney M (2008) Modeling the reactive properties of tandemly activated tRNAs. Org Biomol Chem 6:3292-9
Duca, Maria; Chen, Shengxi; Hecht, Sidney M (2008) Aminoacylation of transfer RNAs with one and two amino acids. Methods 44:87-99
Duca, Maria; Maloney, David J; Lodder, Michiel et al. (2007) Synthesis of bisaminoacylated pdCpAs and tandemly activated transfer RNAs. Bioorg Med Chem 15:4629-42
Maloney, David J; Ghanem, Noha; Zhou, Jia et al. (2007) Positional assignment of differentially substituted bisaminoacylated pdCpAs. Org Biomol Chem 5:3135-8
Choudhury, Ambar K; Golovine, Serguei Y; Dedkova, Larisa M et al. (2007) Synthesis of proteins containing modified arginine residues. Biochemistry 46:4066-76
Fahmi, Nour Eddine; Dedkova, Larisa; Wang, Bixun et al. (2007) Site-specific incorporation of glycosylated serine and tyrosine derivatives into proteins. J Am Chem Soc 129:3586-97
Wang, Bixun; Zhou, Jia; Lodder, Michiel et al. (2006) Tandemly activated tRNAs as participants in protein synthesis. J Biol Chem 281:13865-8
Dedkova, Larisa M; Fahmi, Nour Eddine; Golovine, Serguei Y et al. (2006) Construction of modified ribosomes for incorporation of D-amino acids into proteins. Biochemistry 45:15541-51

Showing the most recent 10 out of 18 publications