Synthesis and testing of peptides for anti-prion activity

Creutzfeldt–Jakob disease (CJD) is one of the fatal transmissible spongiform encephalopathies for which there is no known cure. The disease is associated with an abnormally folded prion protein, PrP-res, which is thought to form due to interaction between normal prion PrPC and PrP-res. Small peptides were designed to prevent this interaction. A structure–activity relationship is described for a series of peptides which were synthesised and tested for their activity against two prion disease model assays, an in vitro cellular assay and an in vitro anti-aggregation polymerisation assay. A number of peptides were found to be active at levels of 100 μM. New libraries were synthesised in order to concentrate on discovering new, shorter peptides which could be leads for developing peptidomimetics.

Graphical abstract This paper describes the design, synthesis and evaluation of small peptides designed to interfere with interaction between PrP-res and PrPSc.Figure optionsDownload full-size imageDownload as PowerPoint slide