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

ABSTRACT: 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.

SUBMITTER: Paschold A 

PROVIDER: S-EPMC9313110 | biostudies-literature |

REPOSITORIES: biostudies-literature