In this highly multidisciplinary project, we will study the polyphilic interactions that determine the specificity of pepstatin-based probes containing fluorinated amino acids for photoaffinity labelling towards plant aspartic proteases. To understand these determinants, we will harness the diversity of aspartic proteases from the model plant Arabidopsis thaliana and deploy chemical synthesis, advanced modelling, protease biochemistry, mass spectrometry and structural analysis methods. A detailed analysis of the consequences of this diversification will lead to an increased understanding of the polyphilic interactions in the active site of the proteases and would boost the development of better probes for aspartic proteases of plants and other organisms.