29/10/2019
Custom bioinfomatic analysis by Dr. Martin Reczko contributed to a collaborative study between BSRC Alexander Fleming, D. Delivora and G. Skretas from the National Hellenic Research Foundation and other partners published in Scientific Advances. A novel highly adaptable bacterial platform for generating molecular libraries with expanded diversity and direct functional screening discovering inhibitors of protein aggregation is introduced. The process of protein misfolding and aggregation is associated with a wide range of human disorders, including Alzheimer’s and Parkinson’s diseases. To increase the effectiveness of drug discovery programmes for these conditions, the -to our knowledge- largest functional screen of small-size molecular entities described to date was performed. More than 400 macrocyclic compounds that efficiently reduce amyloid β peptide aggregation and toxicity both in vitro and in vivo were discovered. Within this collaboration, the Genomics Facility of Fleming conducted high throughput sequencing to test the diversity of the initial peptide library and to determine the entire ensemble of potentially bioactive cyclic heptapeptides present after functional screening. In-house bioinfomatic developments enabled the extraction of all peptide sequence information from the libraries.
DOI: 10.11/sciadv.aax5108
URL: https://advances.sciencemag.org/content/5/10/eaax5108.abstract