Modulating the fibrillization of parathyroid-hormone (PTH) peptides: azo-switches as reversible and catalytic entities

Paschold, A., et al. Biomedicines, 2022, DOI:https://doi.org/10.3390/biomedicines10071512

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. We embed the azobenzene derivate 3-{[(4-aminomethyl)phenyl]diazenyl}benzoic acid (3,4′-AMPB) into the PTH-derived peptide PTH25–37 to generate the artificial peptide AzoPTH25–37 via solid-phase synthesis. The trans-form of AzoPTH25–37 fibrillizes similar to PTH25–37, while the cis-form of AzoPTH25–37 generates only amorphous aggregates. 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.