Synthesis and biological evaluation of non-isomerizable analogues of Ala-tRNA(Ala).
Aminoacyl-tRNAs serve as amino acid donors in many reactions in addition to protein synthesis by the ribosome, including synthesis of the peptidoglycan network in the cell wall of bacterial pathogens. Synthesis of analogs of aminoacylated tRNAs is critical to further improve the mechanism of these reactions. Here we have described the synthesis of two non-isomerizable analogues of Ala-tRNA(Ala) containing an amide bond instead of the isomerizable ester that connects the amino acid with the terminal adenosine in the natural substrate. The non-isomerizable 2' and 3' regioisomers were not used as substrates by FemX(Wv), an alanyl-transferase essential for peptidoglycan synthesis, but inhibited this enzyme with IC50 of 5.8 and 5.5 μM, respectively.
Institut Parisien de Chimie Moléculaire, CNRS UMR 7201, F-75005 Paris, France.
Denia
D
Mellal
Matthieu
M
Fonvielle
Marco
M
Santarem
Maryline
M
Chemama
Yoann
Y
Schneider
Laura
L
Iannazzo
Emmanuelle
E
Braud
Michel
M
Arthur
Mélanie
M
Etheve-Quelquejeu
D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D019884:Nitrogenous Group Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012344:RNA, Transfer, Ala / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D012344:RNA, Transfer, Ala; D019884:Nitrogenous Group Transferases