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 1-84 , a human hormone secreted by the parathyroid glands, is important for the maintenance of extracellular fluid calcium and phosphorus homeostasis. Controlling fibrillization of PTH 1-84 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 25-37 to generate the artificial peptide AzoPTH 25-37 via solid-phase synthesis. AzoPTH 25-37 shows excellent photostability (more than 20 h in the dark) and can be reversibly photoswitched between its cis / trans forms. As investigated by ThT-monitored fibrillization assays, the trans -form of AzoPTH 25-37 fibrillizes similar to PTH 25-37 , while the cis -form of AzoPTH 25-37 generates only amorphous aggregates. Additionally, cis -AzoPTH 25-37 catalytically inhibits the fibrillization of PTH 25-37 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.