title: Synthesis of bisaminoacylated pdCpAs and tandemly activated transfer RNAs.
abstract: Described herein is the preparation of new bisacylated tRNAs and their participation in protein synthesis. It has been reported that Thermus thermophilus phenylalanyl-tRNA synthetase can introduce two phenylalanine moieties onto the 3'-terminal adenosine of its cognate tRNA. It is also possible to prepare bisactivated tRNAs in vitro; these participate in protein synthesis [Wang, B.; Zhou, J.; Lodder, M.; Anderson, R. D.; Hecht, S. M. J. Biol. Chem.2006, 281, 13865]. Presently, the chemical strategy used for the synthesis of the key intermediate bisacylated pdCpAs is described. Bis-S-alanyl- and bis-S-methionyl-pdCpAs were prepared initially. Further, S-threonine, S-allo-threonine, S-homoserine, and (S)-(+)-2-amino-3-hydroxy-3-methylbutyric acid were coupled with the dinucleotide to define preparative methods applicable to more complex amino acids bearing additional functionality in the form of an OH group.
authors.affiliation: Department of Chemistry and Biology, University of Virginia, Charlottesville, VA 22904, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Duca
authors.forename: David J
authors.initials: DJ
authors.lastname: Maloney
authors.forename: Michiel
authors.initials: M
authors.lastname: Lodder
authors.forename: Bixun
authors.initials: B
authors.lastname: Wang
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Hecht
mesh_terms: D000107:Acetylation; D000409:Alanine / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D006714:Homoserine / Q000737:chemistry; D007202:Indicators and Reagents; D008715:Methionine / Q000737:chemistry; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000138:chemical synthesis*; D013762:Tetrahydrofolate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D016963:Thermus thermophilus / Q000737:chemistry; D013912:Threonine / Q000737:chemistry
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D007202:Indicators and Reagents; D013912:Threonine; D006714:Homoserine; D012343:RNA, Transfer; D008715:Methionine; D013762:Tetrahydrofolate Dehydrogenase; D000409:Alanine