May 15, 2017, by Editor
Pharmacy Research Blog Nov 2016 – Jan 2017
Welcome to our research blog, bringing you highlights from the latest edition of the School of Pharmacy Journal, a quarterly collection of publications and press releases.
The images below represent the design and synthesis of nucleotide monophosphate mimetic eIF4E inhibitors, which are discussed in the following recent publication: Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation published in the European Journal of Medicinal Chemistry.
![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,](https://blogs.nottingham.ac.uk/pharmacy/files/2017/05/Journal-sq.jpg)
Fig. 1. (a) mRNA cap recognition (represented by m7GTP shown as yellow CPK sticks) and binding of eIF4G or 4E-BPs
![(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.)](https://blogs.nottingham.ac.uk/pharmacy/files/2017/05/Journal-sq2.jpg)
(b) GMP derivatives with N7-substituents other than methyl
There was a significant research output in terms of publications and grant capture for the period including about 21 publications, some of which highlight research collaboration between the UK and Malaysia campuses.
In the paper “Cudraflavone C Induces Tumor-Specific Apoptosis in Colorectal Cancer Cells through Inhibition of the Phosphoinositide 3-Kinase (PI3K)-AKT Pathway“, a collaborative effort between researchers at two campuses, they conclude that Cudraflavone C is a PI3K-AKT inhibitor with selective anti-tumor activities against CRC cells.
In another paper “Correlating gastric emptying of amphotericin B and paracetamol solid lipid nanoparticles with changes in particle surface chemistry” collaborators conclude that the rate of the diffusion of simulated media into solid lipid nanoparticles depended on the solubility of the loaded-drug in the particular medium.
On 18 January, Dr. Daniel G. Anderson, Massachusetts Institute of Technology, Koch Institute, gave a lecture to about 300 staff and students from across the University. This exciting talk ‘Nucleic acid delivery systems for RNA therapy and gene editing’ was part of the launch of the Inaugural Biomaterials Discovery Workshop which will be held annually at the University, associated with our £6.5M EPSRC Programme Grant in Next Generation Biomaterials.
Professor Phil Williams
Phil.Williams@nottingham.ac.uk
Director of Research and Knowledge Exchange
(Nottingham)
Professor Nashiru Billa
Nashiru.Billa@nottingham.edu.my
Associate Dean (Research)
(Malaysia)
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