Synthesis of bisaminoacylated pdCpAs and tandemly activated transfer RNAs.
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.
Duca
Maria
M
Department of Chemistry and Biology, University of Virginia, Charlottesville, VA 22904, USA.
Maloney
David J
DJ
Lodder
Michiel
M
Wang
Bixun
B
Hecht
Sidney M
SM
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
D000596:Amino Acids; D001426:Bacterial Proteins; D007202:Indicators and Reagents; D013912:Threonine; D006714:Homoserine; D012343:RNA, Transfer; D008715:Methionine; D013762:Tetrahydrofolate Dehydrogenase; D000409:Alanine