Photocontrol and structural analysis of amyloid fibril formation using azobenzene and novel spiropyran photoswitches

Abstract

The self-organization of amyloidogenic peptides plays a crucial role in diseases and in physiological functions. Thus, the control of this process is a powerful tool to gain insights into its kinetics and the structural nature of the peptide assemblies. In this work different photoswitches were incorporated into PTH-derived peptides to establish a model system able to switch between a fibrillary and nonfibrillar state. As switches the azobenzene photoswitch 3-((4-(aminomethyl)phenyl)diazenyl)benzoic acid was chosen and the novel spiropyran building blocks were 5’-amino-1’,3’,3’-trimethylspiro[chromene-2,2’-indoline]-6-carboxylic acid and 6-amino-1’,3’,3’-trimethylspiro[chromene-2,2’-indoline]-5’-carboxylic acid were designed, which can be incorporated into the peptide backbone. The spiropyran building are the first report of spiropyrans introduced into the backbone of peptides. The azobenzene modified peptide were used to establish a switchable amyloid forming model system.