Modulating the Fibrillization of Parathyroid-Hormone (PTH) Peptides: Azo-Switches as Reversible and Catalytic Entities.

We here report a novel strategy to control the bioavailability of the fibrillizing parathyroid hormone (PTH)-derived peptides, where the concentration of the bioactive form is controlled by an reversible, photoswitchable peptide. PTH, a human hormone secreted by the parathyroid glands, is important for the maintenance of extracellular fluid calcium and phosphorus homeostasis. Controlling fibrillization of PTH represents an important approach for in vivo applications, in view of the pharmaceutical applications for this protein. We embed the azobenzene derivate 3-{[(4-aminomethyl)phenyl]diazenyl}benzoic acid (3,4'-AMPB) into the PTH-derived peptide PTH to generate the artificial peptide AzoPTH via solid-phase synthesis. AzoPTH shows excellent photostability (more than 20 h in the dark) and can be reversibly photoswitched between its / forms. As investigated by ThT-monitored fibrillization assays, the -form of AzoPTH fibrillizes similar to PTH, while the -form of AzoPTH generates only amorphous aggregates. Additionally, -AzoPTH catalytically inhibits the fibrillization of PTH in ratios of up to one-fifth. The approach reported here is designed to control the concentration of PTH-peptides, where the bioactive form can be catalytically controlled by an added photoswitchable peptide.