Institut Parisien de Chimie Moléculaire, CNRS UMR 7201, F-75005 Paris, France.
Org Biomol Chem. 2013 Sep 28;11(36):6161-9. doi: 10.1039/c3ob41206g.
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.
氨酰-tRNA 除了通过核糖体参与蛋白质合成外，还可以作为许多反应的氨基酸供体，包括细菌病原体细胞壁中肽聚糖网络的合成。氨酰化 tRNA 类似物的合成对于进一步改善这些反应的机制至关重要。在这里，我们描述了两种非异构化的 Ala-tRNA（Ala）类似物的合成，它们含有酰胺键而不是天然底物中连接氨基酸和末端腺苷的可异构化酯。非异构化的 2'和 3' 区域异构体不能被 FemX（Wv）用作底物，FemX（Wv）是一种参与肽聚糖合成的必需丙氨酰转移酶，但分别以 5.8 和 5.5 μM 的 IC50 抑制该酶。
