Abstract

The long-term goal is the elaboration and study of proteins containing synthetic amino acids at specific, predetermined positions and the kinetics of there enzyme reactions These are to be incorporated by read throug of nonsense codons with misacylated suppressor tRNAs. It is proposed to continue the preparation and study of analogs of E. coli dihydrofolate reductase, firefly luciferase and HIV-1 protease. Also proposed for study are methods that have the potential to increase the efficiency of synthesis of the analogs of interest, as well as the repertoire of amino acid analogs that can be incorporated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA077359-01
Application #
2564652
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Beisler, John A
Project Start
1998-04-01
Project End
2003-01-31
Budget Start
1998-04-01
Budget End
1999-01-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Virginia
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001910777
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