In silico exploration of the Embryonic Lethal Abnormal Vision protein-mRNA interaction followed by in vitro bioassays for the identification of peptides potentially useful in neurodegenerative diseases treatment

1. Introduction The Embryonic Lethal Abnormal Vision (ELAV) proteins are RNA-Binding Proteins that, in response to intra- and extracellular signals, bind preferentially to the Adenineuracile Rich Elements (ARE) of target mRNAs affecting their stability and rate of translation. Recently, we studied for the first time the ELAV-mRNA system from a medicinal chemistry point of view by evaluating the effect of four peptides-corresponding to the sequences of ELAV proteins primarily involved in the binding to ARE-mRNA- on the stability of VEGF and NOVA-1 transcripts. Biological results clearly showed ELAV-like properties for the equimolar mixture of the peptides.1 2. Results and Discussion To explore the chemical features directly involved in the binding of the ELAV protein HuD with target mRNAs (Figure 1), we studied in silico the HuD-mRNA complex by means of molecular dynamics simulations. In vitro bioassay results, obtained testing peptides either individually or in couples, confirmed the molecular modelling predictions.