期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 19, 期 7, 页码 1921-1925出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2009.02.053
关键词
5 ' mRNA cap analogs; Phosphorothioate; Inhibition of translation; Translation initiation factor eIF4E; Decapping Scavenger DcpS; Nucleotide synthesis
资金
- Howard Hughes Medical Institute [55005604]
- National Science Support [PBZMNiSW07/I/2007]
We report synthesis and properties of a pair of new potent inhibitors of translation, namely two diastereomers of 7-methylguanosine 5'-(1-thiotriphosphate). These new analogs of mRNA 5'cap (referred to as m(7)GTP alpha S (D1) and (D2)) are recognized by translational factor eIF4E with high affinity and are not susceptible to hydrolysis by Decapping Scavenger pyrophosphatase (DcpS). The more potent of diastereomers, m7GTPaS (D1), inhibited cap-dependent translation in rabbit reticulocyte lysate similar to 8-fold and similar to 15-fold more efficiently than m(7)GTP and m(7)GpppG, respectively. Both analogs were also significantly more stable in RRL than unmodified ones. (C) 2009 Elsevier Ltd. All rights reserved.
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