Structure-guided design, synthesis, and evaluation of guanine-derived inhibitors of the eIF4E mRNA–cap interaction

X Chen, DJ Kopecky, J Mihalic, S Jeffries…

Index: Chen, Xiaoqi; Kopecky, David J.; Mihalic, Jeff; Jeffries, Shawn; Min, Xiaoshan; Heath, Julie; Deignan, Jeff; Lai, Sujen; Fu, Zice; Guimaraes, Cristiano; Shen, Shanling; Li, Shyun; Johnstone, Sheree; Thibault, Stephen; Xu, Haoda; Cardozo, Mario; Shen, Wang; Walker, Nigel; Kayser, Frank; Wang, Zhulun Journal of Medicinal Chemistry, 2012 , vol. 55, # 8 p. 3837 - 3851

Full Text: HTML

Citation Number: 62

Abstract

The eukaryotic initiation factor 4E (eIF4E) plays a central role in the initiation of gene translation and subsequent protein synthesis by binding the 5′ terminal mRNA cap structure. We designed and synthesized a series of novel compounds that display potent binding affinity against eIF4E despite their lack of a ribose moiety, phosphate, and positive charge as present in m7-GMP. The biochemical activity of compound 33 is 95 nM for ...