The goal of this article is to overview the current understanding of biomolecule-inorganic materials interactions; to identify the 'rules' that govern interaction; to highlight the drawbacks of the present approaches and outline future challenges and opportunities.Please check this proof carefully. Our staff will not read it in detail after you have returned it. Translation errors between word-processor files and typesetting systems can occur so the whole proof needs to be read. Please pay particular attention to: tabulated material; equations; numerical data; figures and graphics; and references. If you have not already indicated the corresponding author(s) please mark their name(s) with an asterisk. Please e-mail a list of corrections or the PDF with electronic notes attached -do not change the text within the PDF file or send a revised manuscript.Please bear in mind that minor layout improvements, e.g. in line breaking, table widths and graphic placement, are routinely applied to the final version.We will publish articles on the web as soon as possible after receiving your corrections; no late corrections will be made.Please return your final corrections, where possible within 48 hours of receipt, by e-mail to: proofs@rsc.org Electronic (PDF) reprints will be provided free of charge to the corresponding author. Enquiries about purchasing paper reprints should be addressed via: http://www.rsc.org/Publishing/ReSourCe/PaperReprints/. Costs for reprints are below: Interactions between inorganic materials and biomolecules at the molecular level, although complex, are commonplace. Examples include biominerals, which are, in most cases, facilitated by and in contact with biomolecules; implantable biomaterials; and food and drug handling. The effectiveness of these functional materials is dependant on the interfacial properties i.e. the extent of molecular level 'association' with biomolecules. The goal of this overview is four-fold: to present biomolecule-inorganic materials interactions and our current understanding using selected examples; to elaborate on approaches that have been used to expose the mechanisms underpinning such interactions; to identify the 'rules' or 'guiding principles' that govern interactions that could be used to explain and hence predict behaviour; and finally to highlight the drawbacks of the present approaches and outline future challenges and opportunities. Reprint costs

Eukaryotic translation initiation factor 4E (eIF4E) is considered as the corner stone in the cap-dependent translation initiation machinery. Its role is to recruit mRNA to the ribosome through recognition of the 5′-terminal mRNA cap structure (m7GpppN, where G is guanosine, N is any nucleotide). eIF4E is implicated in cell transformation, tumourigenesis, and angiogenesis by facilitating translation of oncogenic mRNAs; it is thus regarded as an attractive anticancer drug target. We have used two approaches to design cap-binding inhibitors of eIF4E by modifying the N7-substituent of m7GMP and replacing the phosphate group with isosteres such as squaramides, sulfonamides, and tetrazoles, as well as by structure-based virtual screening aimed at identifying non-nucleotide cap-binding antagonists. Phosphomimetic nucleotide derivatives and highly ranking virtual hits were evaluated in a series of in vitro and cell-based assays to identify the first non-nucleotide eIF4E cap-binding inhibitor with activities in cell-based assays, N-[(5,6-dihydro-6-oxo-1,3-dioxolo[4,5-g]quinolin-7-yl)methyl]-N′-(2-methyl-propyl)-N-(phenyl-methyl)thiourea (14), including down-regulation of oncogenic proteins and suppression of RNA incorporation into polysomes. Although we did not observe cellular activity with any of our modified m7GMP phosphate isostere compounds, we obtained X-ray crystallography structures of three such compounds in complex with eIF4E, 5′-deoxy-5′-(1,2-dioxo-3-hydroxycyclobut-3-en-4-yl)amino-N7-methyl-guanosine (4a), N7-3-chlorobenzyl-5′-deoxy-5′-(1,2-dioxo-3-hydroxy-cyclobut-3-en-4-yl)amino-guanosine (4f), and N7-benzyl-5′-deoxy-5′-(trifluoromethyl-sulfamoyl)guanosine (7a). Collectively, the data we present on structure-based design of eIF4E cap-binding inhibitors should facilitate the optimisation of such compounds as potential anticancer agents.

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