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(b) GMP derivatives with N7-substituents other than methyl, such as 4-fluorobenzyl [24] (green) or (4-chlorophenoxy)ethyl [20] (cyan), also make hydrophobic contacts with two concave lipophilic pockets (surface representations) behind the W56eW102 stack. Figure constructed from PDB entries 2V8W, 2V8Y, 4DT6, and 4TPW. 3D-Structure illustrations in this and subsequent Figures were prepared using MacPyMOL (The PyMOL Molecular Graphics System, Version 1.2, Schr€odinger, LLC). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)Fig. 1. (a) mRNA cap recognition (represented by m7GTP shown as yellow CPK sticks) and binding of eIF4G or 4E-BPs (represented by a peptide derived from 4E-BP1 shown as a cyan cartoon) occurs on opposite faces of eIF4E (green cartoon). Apart from direct cap-binding antagonists, allosteric inhibitors (binding pose of 4-EGI1 [22] shown as magenta sticks) and inhibitors derived from eIF4G and 4E-BPs [23] are being developed. Whereas m7GTP-binding is dominated by polar interactions between the cationic N-methylpurine system and eIF4E residues W56, W102, and E103 (cationep interaction and H-bonds), as well as the phosphate groups with residues R157, K159, and K162,